ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.4136+1G>A (rs1562928997)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000757809 SCV000886285 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000757809 SCV001467948 likely pathogenic Cystic fibrosis 2020-12-11 criteria provided, single submitter clinical testing Variant summary: CFTR c.4136+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict that the variant abolishes a 5-prime splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251168 control chromosomes (gnomAD). c.4136+1G>A has been reported in the literature as homozygous in at least one individual affected with Cystic Fibrosis (e.g. Feuillet-Fieux_2004) . These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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