VCV000048684.28 - ClinVar

NM_000492.4(CFTR):c.313del (p.Ile105fs)

Germline

Reviewed by expert panel

Reviewed by expert panel. Learn more about how ClinVar calculates review status.

Pathogenic

for Cystic fibrosis

Classification is based on the expert panel submission

Mar 2017 by CFTR2

The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000492.4(CFTR):c.313del (p.Ile105fs)

Variation ID: 48684 Accession: VCV000048684.28

Type and length

Deletion, 1 bp

Location

Cytogenetic: 7q31.2 7: 117530937 (GRCh38) [ NCBI UCSC ] 7: 117170991 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 12, 2017	Apr 4, 2026	Mar 17, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.313del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Ile105fs	frameshift
NM_000492.3:c.313delA
NC_000007.14:g.117530938del
NC_000007.13:g.117170992del
NG_016465.4:g.70155del
LRG_663:g.70155del

... more HGVS ... less HGVS

Protein change

Other names

444delA
c.313delA
p.Ile105Serfs*2

Canonical SPDI

NC_000007.14:117530936:AA:A

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA327059 dbSNP: rs121908801 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CFTR		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	3950	6460

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Cystic fibrosis	Pathogenic (5)	reviewed by expert panel	Mar 17, 2017	RCV000046792.21
not provided	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Aug 5, 2024	RCV000759763.9
Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis	Pathogenic (1)	criteria provided, single submitter	-	RCV001004425.1
CFTR-related disorder	Pathogenic (1)	criteria provided, single submitter	Aug 4, 2025	RCV001027892.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 17, 2017) C Contributing to aggregate classification	reviewed by expert panel (Sosnay PR et al. (Nat Genet 2013))	Cystic fibrosis	CFTR2 Study: CFTR2 Accession: SCV000245889.2 First in ClinVar: Sep 23, 2015 Last updated: Dec 12, 2017	Other databases https://cftr2.org https://cftr2.org Observation: 1 Collection method: research Allele origin: germline Affected status: yes Observation 1 Collection method: research Allele origin: germline Affected status: yes

Pathogenic (-) N Not contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis	Baylor Genetics Accession: SCV001163469.1 First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Nov 12, 2019) N Not contributing to aggregate classification	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))	Cystic fibrosis	Myriad Genetics, Inc. Accession: SCV001193909.2 First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020	Publications: PubMed (4) PubMed: 15176679‚ 1710600‚ 9003508‚ 9150159 Comment: show NM_000492.3(CFTR):c.313delA(I105Sfs2, aka 444delA) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 15176679, 1710600, 9150159 and 9003508. Classification of NM_000492.3(CFTR):c.313delA(I105Sfs2, aka 444delA) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.â€šÃ„Ã¶âˆšÃ‘âˆšÂ£ (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Sep 10, 2023) N Not contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Cystic fibrosis	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001580421.6 First in ClinVar: May 10, 2021 Last updated: Feb 15, 2026	Publications: PubMed (6) PubMed: 1695717‚ 1710600‚ 26208274‚ 28546993‚ 7691345‚ 9725922 Comment: show For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 48684). This variant is also known as 444delA. This premature translational stop signal has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 1710600, 26208274, 28546993). This variant is present in population databases (rs779091180, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Ile105Serfs*2) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Mar 08, 2020) N Not contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Cystic fibrosis	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001339216.1 First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020	Publications: PubMed (3) PubMed: 15176679‚ 26208274‚ 28546993 Comment: show Variant summary: CFTR c.313delA (p.Ile105SerfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251136 control chromosomes (gnomAD). c.313delA has been reported in the literature, in compound heterozygous or homozygous state, in multiple individuals affected with Cystic Fibrosis (e.g. Behar_2017, Decaestecker_2004, Siryani_2015). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters including an expert panel (CFTR2) (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Oct 12, 2017) N Not contributing to aggregate classification	criteria provided, single submitter (Quest Diagnostics criteria)	not provided	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000889308.2 First in ClinVar: Mar 14, 2019 Last updated: Jan 01, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Nov 23, 2022) N Not contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cystic fibrosis	Johns Hopkins Genomics, Johns Hopkins University Accession: SCV003839135.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 05, 2024) N Not contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV004226567.2 First in ClinVar: Jan 06, 2024 Last updated: Dec 28, 2024	Publications: PubMed (10) PubMed: 1710600‚ 18456578‚ 26282188‚ 26708955‚ 28546993‚ 28944235‚ 31036917‚ 34782259‚ 37310422‚ 37980178 Comment: show PP5, PM2, PM3, PVS1 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 04, 2025) N Not contributing to aggregate classification	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	CFTR-related disorders	Natera, Inc. Accession: SCV001190614.2 First in ClinVar: Mar 29, 2020 Last updated: Apr 04, 2026	Publications: PubMed (3) PubMed: 15176679‚ 26208274‚ 27034411 Comment: show The c.313delA variant in CFTR is a frameshift variant predicted to shift the reading frame beginning at codon 105 and leads to a stop codon 2 codons downstream. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 26208274, 15176679, 27034411). Given the available evidence, this variant is classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001742759.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Study: VKGL Data-share Consensus Accession: SCV001954659.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

NM_000492.3(CFTR):c.313delA(I105Sfs*2, aka 444delA) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 15176679, 1710600, 9150159 and 9003508. Classification of NM_000492.3(CFTR):c.313delA(I105Sfs*2, aka 444delA) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.â€šÃ„Ã¶âˆšÃ‘âˆšÂ£

Comment:

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 48684). This variant is also known as 444delA. This premature translational stop signal has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 1710600, 26208274, 28546993). This variant is present in population databases (rs779091180, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Ile105Serfs*2) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922).

Comment:

Variant summary: CFTR c.313delA (p.Ile105SerfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251136 control chromosomes (gnomAD). c.313delA has been reported in the literature, in compound heterozygous or homozygous state, in multiple individuals affected with Cystic Fibrosis (e.g. Behar_2017, Decaestecker_2004, Siryani_2015). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters including an expert panel (CFTR2) (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

The c.313delA variant in CFTR is a frameshift variant predicted to shift the reading frame beginning at codon 105 and leads to a stop codon 2 codons downstream. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 26208274, 15176679, 27034411). Given the available evidence, this variant is classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The new face of cystic fibrosis in the era of population genetic carrier screening.	Dotan M	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2024	PMID: 37980178
Updated recommendations for CFTR carrier screening: A position statement of the American College of Medical Genetics and Genomics (ACMG).	Deignan JL	Genetics in medicine : official journal of the American College of Medical Genetics	2023	PMID: 37310422
Complete CFTR gene sequencing in 5,058 individuals with cystic fibrosis informs variant-specific treatment.	Raraigh KS	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2022	PMID: 34782259
Sequencing as a first-line methodology for cystic fibrosis carrier screening.	Beauchamp KA	Genetics in medicine : official journal of the American College of Medical Genetics	2019	PMID: 31036917
Assessing risk for Mendelian disorders in a Bronx population.	diSibio G	Molecular genetics & genomic medicine	2017	PMID: 28944235
Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening.	Behar DM	Molecular genetics & genomic medicine	2017	PMID: 28546993
Modeling Cystic Fibrosis Using Pluripotent Stem Cell-Derived Human Pancreatic Ductal Epithelial Cells.	Simsek S	Stem cells translational medicine	2016	PMID: 27034411
The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing.	Schrijver I	The Journal of molecular diagnostics : JMD	2016	PMID: 26708955
CFTR genotype-related body water and electrolyte balance during a marathon.	Del Coso J	Scandinavian journal of medicine & science in sports	2016	PMID: 26282188
Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations in a Cohort of Patients Residing in Palestine.	Siryani I	PloS one	2015	PMID: 26208274
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice.	Castellani C	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2008	PMID: 18456578
Genotype/phenotype correlation of the G85E mutation in a large cohort of cystic fibrosis patients.	Decaestecker K	The European respiratory journal	2004	PMID: 15176679
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.	Cohn JA	The New England journal of medicine	1998	PMID: 9725922
Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%.	Macek M Jr	American journal of human genetics	1997	PMID: 9150159
Characterization of more than 85% of cystic fibrosis alleles in the Greek population, including five novel mutations.	Tzetis M	Human genetics	1997	PMID: 9003508
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.	Yang Y	Human molecular genetics	1993	PMID: 7691345
Detection of three rare frameshift mutations in the cystic fibrosis gene in an African-American (CF444delA), an Italian (CF2522insC), and a Soviet (CF3821delT).	White MB	Genomics	1991	PMID: 1710600
A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.	Cutting GR	Nature	1990	PMID: 1695717
https://cftr2.org	-	-	-	-
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Text-mined citations for rs121908801 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 04, 2026