ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1584+12T>C (rs193922502)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000250540 SCV000052130 uncertain significance not specified 2020-12-22 criteria provided, single submitter clinical testing Variant summary: CFTR c.1584+12T>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 0.00022 in 252294 control chromosomes (gnomAD and publication data). This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Chronic Pancreatitis Risk (0.00022 vs 0.0063), allowing no conclusion about variant significance. c.1584+12T>C has been reported in the literature in individuals affected with CF and CBAVD (Ivaschenko_1993, Zielenski_1995), however it was also found in controls (Rosendahl_2012). These reports do not provide unequivocal conclusions about association of the variant with Chronic Pancreatitis Risk. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics,PreventionGenetics RCV000250540 SCV000304476 likely benign not specified criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985676 SCV001134115 uncertain significance not provided 2019-07-23 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001163393 SCV001325425 uncertain significance CFTR-related disorders 2017-06-12 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.
Invitae RCV001414754 SCV001616895 likely benign Cystic fibrosis 2020-11-24 criteria provided, single submitter clinical testing

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