ClinVar

Description

Variant summary: CFTR c.4242+10T>C alters a conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation 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 0.00038 in 281870 control chromosomes (gnomAD), predominantly at a frequency of 0.004 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in CFTR causing Cystic Fibrosis (0.00038 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. The following publications have been ascertained in the context of this evaluation (PMID: 28040058, 28408918, 11379874, 25087612). ClinVar contains an entry for this variant (Variation ID: 53928). Based on the evidence outlined above, the variant was classified as likely benign.