NM_000492.4(CFTR):c.1585-1G>A AND CFTR-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 17, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001027893.10

Allele description [Variation Report for NM_000492.4(CFTR):c.1585-1G>A]

NM_000492.4(CFTR):c.1585-1G>A

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
LOC111674475:CFTR intron 11 enhancer [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.1585-1G>A

Other names:

1717-1G->A; 1717-1>A

HGVS:

NC_000007.14:g.117587738G>A
NG_016465.4:g.126955G>A
NG_056131.3:g.693G>A
NM_000492.3(CFTR):c.1585-1G>A
NM_000492.4:c.1585-1G>AMANE SELECT
LRG_663t1:c.1585-1G>A
LRG_663:g.126955G>A
NC_000007.13:g.117227792G>A
NM_000492.3:c.1585-1G>A
NM_000492.4:c.1585-1G>A

Nucleotide change:

1717-1G>A

Links:

Genetic Testing Registry (GTR): GTR000074114; Genetic Testing Registry (GTR): GTR000500233; OMIM: 602421.0008; dbSNP: rs76713772

Molecular consequence:

NM_000492.4:c.1585-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: CFTR-related disorder (CFTR-RD)
Synonyms:: CFTR-related disorders; CFTR-related condition
Identifiers:: MONDO: MONDO:7770004; MedGen: C5924204

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001190615	Natera, Inc.	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	Pathogenic (Jul 17, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25688174, 16046196, 25583415 Citation Link,
SCV004114468	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001190615

Natera, Inc.

criteria provided, single submitter

(Natera Variant Classification Schema (03/2026))

Pathogenic
(Jul 17, 2025)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV004114468

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Next generation sequencing to determine the cystic fibrosis mutation spectrum in Palestinian population.

Essawi O, Farraj M, De Leeneer K, Steyaert W, De Pauw K, De Paepe A, Claes K, Essawi T, Coucke PJ.

Dis Markers. 2015;2015:458653. doi: 10.1155/2015/458653. Epub 2015 Jan 26.

PubMed [citation]

PMID:: 25688174
PMCID:: PMC4321085

MBL2 polymorphisms screening in a regional Italian CF Center.

Trevisiol C, Boniotto M, Giglio L, Poli F, Morgutti M, Crovella S.

J Cyst Fibros. 2005 Sep;4(3):189-91.

PubMed [citation]

PMID:: 16046196

See all PubMed Citations (4)

Details of each submission

From Natera, Inc., SCV001190615.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.1585-1G>A variant in CFTR is a canonical splice acceptor site variant predicted to affect pre-mRNA splicing, which may result in an abnormal transcript and altered protein product. 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: 25688174, 16046196, 25583415). Given the available evidence, this variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV004114468.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The CFTR c.1585-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant, previously described as c.1717-1G>A, is known to be causative for cystic fibrosis (see for example Kerem et al. 1990. PubMed ID: 2236053; Sosnay et al. 2013. PubMed ID: 23974870). This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-117227792-G-A). Variants that disrupt the consensus splice acceptor site in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 4, 2026

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