ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.4242+1G>T

gnomAD frequency: 0.00001  dbSNP: rs372227120
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000047115 SCV000245880 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000047115 SCV000220902 likely pathogenic Cystic fibrosis 2014-11-20 criteria provided, single submitter literature only
Mendelics RCV000047115 SCV000886248 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004307 SCV001163184 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000047115 SCV002573960 pathogenic Cystic fibrosis 2022-09-05 criteria provided, single submitter curation This variant was identified in 2 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1_STR, PS1_SUP, PM2_SUP, PM3_VSTR, PP4
Ambry Genetics RCV000047115 SCV002628642 pathogenic Cystic fibrosis 2015-09-16 criteria provided, single submitter clinical testing The c.4242+1G>T intronic pathogenic mutation (also known as 4374+1G>T) results from a G to T substitution one nucleotide after coding exon 26 of the CFTR gene. This alteration was reported in one patient with cystic fibrosis who had pancreatic insufficiency, elevated sweat chloride levels, and decreased lung function (Dork et al. Genomics. 1993 Mar;15(3):688-91). This individual also had the deltaF508 mutation, however phase was unknown. In addition to the clinical data presented in the literature, since alterations that disrupt the canonical splice donor site are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Invitae RCV000047115 SCV003269740 pathogenic Cystic fibrosis 2023-11-24 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 26 of the CFTR gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs372227120, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with cystic fibrosis (PMID: 1379210, 7682196, 15074370). This variant is also known as 4374+1G>T. ClinVar contains an entry for this variant (Variation ID: 53930). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001831791 SCV002075956 pathogenic CFTR-related disorders 2017-03-17 no assertion criteria provided clinical testing

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