ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.4242+10T>C (rs138642693)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080172 SCV000075126 benign Cystic fibrosis 2020-11-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000079004 SCV000110873 benign not specified 2013-05-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000079004 SCV000697014 uncertain significance not specified 2021-04-22 criteria provided, single submitter clinical testing Variant summary: CFTR c.4242+10T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00034 in 250468 control chromosomes, predominantly at a frequency of 0.0048 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (0.00034 vs 0.013), allowing no conclusion about variant significance. c.4242+10T>C has been reported in the literature in individuals screened for Cystic Fibrosis or other CFTR-related disorders (e.g. Marechal_2001, El-Seedy_2016). These reports do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign (n=1) and uncertain signifiance (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV001158877 SCV001320540 uncertain significance CFTR-related disorders 2017-04-28 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.
Natera, Inc. RCV001080172 SCV001460120 uncertain significance Cystic fibrosis 2018-03-23 no assertion criteria provided clinical testing

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