Submissions for variant NM_000492.4(CFTR):c.274-6T>C

gnomAD frequency: 0.00046  dbSNP: rs371315549

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231663	SCV000285000	likely benign	Cystic fibrosis	2024-12-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000248062	SCV000304484	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000590190	SCV000332295	uncertain significance	not provided	2018-07-09	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000248062	SCV000538670	likely benign	not specified	2016-04-25	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Not reported. No information available. Gene not associated to pt disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590190	SCV000603006	likely benign	not provided	2021-01-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590190	SCV000696919	likely benign	not provided	2016-06-19	criteria provided, single submitter	clinical testing	Variant summary: The c.274-6T>C in CFTR gene is an intronic variant that affects a non-conserved nucleotide located at a position not widely known to affect splicing. 5/5 in silico tools predict no significant effects on splicing and these predictions been confirmed by in vitro/vivo studies (Raynal , 2013). Variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.0005 (59/114809 chrs tested) predominantly in individuals of Non-Finnish European ancestry. Although the observed frequency does not exceed the maximal expected allele frequency of a disease causing allele (0.006), it is more than carrier frequency of all known splice acceptor mutations in ExAC cohort, indicating it is rare polymorphism. The variant was reported in several CF-RD spectrum patients without strong evidence for pathogenicity as well as in unaffected controls. Clinical diagnostic centers classify variant as Benign/VUS without evidence to independently evaluate. Taking together, the variant was classified as Likely Benign.
Mendelics	RCV000231663	SCV000886361	benign	Cystic fibrosis	2023-08-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001161754	SCV001323655	uncertain significance	CFTR-related disorder	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000590190	SCV001470300	likely benign	not provided	2022-05-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000590190	SCV001816633	likely benign	not provided	2020-02-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32429104, 10571949, 10601093, 10746558, 11938439, 21499205, 23381846, 21708286, 20717170, 15858154, 21198395, 7691344, 21520337, 25087612, 25781545, 25525159, 17020467, 15758663)
Genome-Nilou Lab	RCV000231663	SCV001821988	likely benign	Cystic fibrosis	2021-07-22	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257533	SCV002529704	likely benign	Hereditary pancreatitis	2021-08-03	criteria provided, single submitter	curation
Ambry Genetics	RCV000231663	SCV002749442	likely benign	Cystic fibrosis	2019-01-22	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.
Johns Hopkins Genomics, Johns Hopkins University	RCV000231663	SCV003839064	likely benign	Cystic fibrosis	2023-02-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590190	SCV004032765	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	CFTR: BP4
Natera, Inc.	RCV000231663	SCV001453946	likely benign	Cystic fibrosis	2019-08-07	no assertion criteria provided	clinical testing