ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.3468+6T>C (rs547442588)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664596 SCV000788586 uncertain significance Cystic fibrosis 2016-12-28 criteria provided, single submitter clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000664596 SCV001164323 uncertain significance Cystic fibrosis 2020-02-19 criteria provided, single submitter clinical testing A heterozygous splice site variation in intron 21 of the CFTR gene was detected. The observed variant c.3468+6T>C has been reported in ClinVar as variant of uncertain significance previously. The variant is found to have allele frequency of <0.1% in the gnomAD database. In summary, the variant meets our criteria to be classified as a variant of unknown significance.
Integrated Genetics/Laboratory Corporation of America RCV001192463 SCV001360600 uncertain significance not specified 2019-10-25 criteria provided, single submitter clinical testing Variant summary: CFTR c.3468+6T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/5 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 4.8e-05 in 250594 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (4.8e-05 vs 0.013), allowing no conclusion about variant significance. c.3468+6T>C has been reported in the literature in an individual affected with Cystic Fibrosis (Ashavaid_2012, Deepak_2012). 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. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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