VCV000054064.15 - ClinVar

NM_000492.4(CFTR):c.828C>A (p.Cys276Ter)

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.828C>A (p.Cys276Ter)

Variation ID: 54064 Accession: VCV000054064.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117536632 (GRCh38) [ NCBI UCSC ] 7: 117176686 (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	Mar 29, 2015	Feb 15, 2026	Mar 17, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.828C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Cys276Ter	nonsense
NC_000007.14:g.117536632C>A
NC_000007.13:g.117176686C>A
NG_016465.4:g.75849C>A
LRG_663:g.75849C>A
LRG_663t1:c.828C>A	LRG_663p1:p.Cys276Ter

... more HGVS ... less HGVS

Protein change

C276*

Other names

Canonical SPDI

NC_000007.14:117536631:C: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.

The Genome Aggregation Database (gnomAD), exomes 0.00000

Links

ClinGen: CA327661 dbSNP: rs397508799 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	3798	6213

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 (4)	reviewed by expert panel	Mar 17, 2017	RCV000047263.19
CFTR-related disorder	Pathogenic (1)	no assertion criteria provided	Mar 17, 2017	RCV001826699.1
Bronchiectasis with or without elevated sweat chloride 1	Pathogenic (1)	criteria provided, single submitter	Dec 31, 2023	RCV004566889.1

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: SCV000245895.2 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 (Dec 31, 2023) N Not contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Bronchiectasis with or without elevated sweat chloride 1	Baylor Genetics Accession: SCV005057455.1 First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024	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 (Jul 05, 2022) N Not contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Cystic fibrosis	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002245864.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 15, 2026	Publications: PubMed (5) PubMed: 1695717‚ 31245908‚ 7541510‚ 7691345‚ 9725922 Comment: show For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54064). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 7541510, 31245908). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Cys276*) 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 15, 2023) N Not contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cystic fibrosis	Ambry Genetics Accession: SCV003911054.3 First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024	Publications: PubMed (3) PubMed: 12752573‚ 7541510‚ 9003508 Comment: show The p.C276* pathogenic mutation (also known as c.828C>A), located in coding exon 7 of the CFTR gene, results from a C to A substitution at nucleotide position 828. This changes the amino acid from a cysteine to a stop codon within coding exon 7. This mutation has been identified in Italian and Greek cohorts of cystic fibrosis patients; however, genotypic and phenotypic information was limited (Férec C et al. Mol Cell Probes, 1995 Apr;9:135-7; Tzetis M et al. Hum Genet, 1997 Jan;99:121-5; Kanavakis E et al. Clin Genet, 2003 May;63:400-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (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 17, 2017) N Not contributing to aggregate classification	no assertion criteria provided	CFTR-related disorders	Natera, Inc. Accession: SCV002078144.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 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

Likely pathogenic (Jul 23, 2014) N Not contributing to aggregate classification	no assertion criteria provided	Cystic fibrosis (Autosomal recessive inheritance)	Counsyl Accession: SCV000220542.3 First in ClinVar: Mar 29, 2015 Last updated: Jul 05, 2025	Publications: PubMed (2) PubMed: 7541510‚ 9003508 Comment: show This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less) Observation: 1 Collection method: literature only Allele origin: unknown Affected status: unknown Observation 1 Collection method: literature only Allele origin: unknown Affected status: unknown

Comment:

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54064). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 7541510, 31245908). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Cys276*) 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:

The p.C276* pathogenic mutation (also known as c.828C>A), located in coding exon 7 of the CFTR gene, results from a C to A substitution at nucleotide position 828. This changes the amino acid from a cysteine to a stop codon within coding exon 7. This mutation has been identified in Italian and Greek cohorts of cystic fibrosis patients; however, genotypic and phenotypic information was limited (Férec C et al. Mol Cell Probes, 1995 Apr;9:135-7; Tzetis M et al. Hum Genet, 1997 Jan;99:121-5; Kanavakis E et al. Clin Genet, 2003 May;63:400-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Identification of 99% of CFTR gene mutations in Bulgarian-, Bulgarian Turk-, and Roma cystic fibrosis patients.	Petrova G	Molecular genetics & genomic medicine	2019	PMID: 31245908
Cystic fibrosis in Greece: molecular diagnosis, haplotypes, prenatal diagnosis and carrier identification amongst high-risk individuals.	Kanavakis E	Clinical genetics	2003	PMID: 12752573
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.	Cohn JA	The New England journal of medicine	1998	PMID: 9725922
Characterization of more than 85% of cystic fibrosis alleles in the Greek population, including five novel mutations.	Tzetis M	Human genetics	1997	PMID: 9003508
Identification of six novel CFTR mutations in a sample of Italian cystic fibrosis patients.	Férec C	Molecular and cellular probes	1995	PMID: 7541510
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.	Yang Y	Human molecular genetics	1993	PMID: 7691345
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	-	-	-	-

Text-mined citations for rs397508799 ...

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 Feb 15, 2026