Description
Variant summary: CFTR c.529A>T (p.Ile177Phe) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250720 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.529A>T has been reported in one heterozygous individual affected with Cystic Fibrosis, another heterozygous patient with bronchitis, with no second alleles reported and without evidence for causality, and in one heterozygous COPD patient (example: Khan_2010, Derichs_2009, Saferali_2022). These report(s) 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: 20627915, 30979466, 34996830). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |