Submissions for variant NM_000492.4(CFTR):c.3139+8A>G

gnomAD frequency: 0.00001  dbSNP: rs193922517

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029518	SCV000052169	uncertain	Cystic fibrosis	2011-08-18	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Counsyl	RCV000029518	SCV000791780	uncertain significance	Cystic fibrosis	2017-05-23	criteria provided, single submitter	clinical testing
Invitae	RCV000029518	SCV001000951	likely benign	Cystic fibrosis	2024-01-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000029518	SCV002607647	likely benign	Cystic fibrosis	2022-10-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003114205	SCV003800475	uncertain significance	not provided	2022-03-31	criteria provided, single submitter	clinical testing	The CFTR c.3139+8A>G variant (rs193922517) is reported in the literature in an individual with borderline sweat chloride levels (Schrijver 2005). This variant is reported in ClinVar (Variation ID: 35863) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor splice, however these predictors are not considered high quality. However, given the lack of clinical and functional data, the significance of the c.3139+8A>G variant is uncertain at this time. References: Schrijver I et al. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. J Mol Diagn. 2005 May;7(2):289-99. PMID: 15858154.
PreventionGenetics, part of Exact Sciences	RCV004532408	SCV004717475	likely benign	CFTR-related disorder	2023-09-05	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).