ClinVar

Description

Variant summary: CFTR c.1950C>A (p.Phe650Leu) results in a non-conservative amino acid change located in the CFTR regulator domain (IPR025837) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251026 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1950C>A has been reported in the literature in one individual with bronchiectasis who had normal sweat chloride levels (Ziedalski_2006). It has also been reported in individuals with unrelated/unspecified phenotypes (e.g. Qiu_2017, Ni_2022). 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: 35313924, 28027573, 17035430). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.