ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.869+8G>T

gnomAD frequency: 0.00002  dbSNP: rs773933167
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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 RCV000780131 SCV000917175 uncertain significance not specified 2018-02-19 criteria provided, single submitter clinical testing Variant summary: CFTR c.869+8G>T 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. 5/5 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 1.2e-05 in 245716 control chromosomes. This frequency is not higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (1.2e-05 vs ND), allowing no conclusion about variant significance. The c.869+8G>T variant has been reported in the literature in compound heterozygosity with the pathogenic variant p.G542X in one hyper-trypsinogenemic infant who had no Cystic Fibrosis manifestations (Prach 2013). This report does 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001272233 SCV001597039 likely benign Cystic fibrosis 2023-08-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001272233 SCV001822026 uncertain significance Cystic fibrosis 2021-07-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV001272233 SCV003855881 likely benign Cystic fibrosis 2022-12-27 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV001272233 SCV001454035 uncertain significance Cystic fibrosis 2020-09-16 no assertion criteria provided clinical testing

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