ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.371+17G>A

gnomAD frequency: 0.00797  dbSNP: rs78645318
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000124098 SCV000167507 benign not specified 2013-08-04 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000124098 SCV001363278 benign not specified 2019-09-03 criteria provided, single submitter clinical testing Variant summary: CACNA1C c.371+17G>A 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. Several computational tools predict a significant impact on normal splicing: five predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0023 in 274692 control chromosomes, predominantly within the African or African-American subpopulation at a frequency of 0.025, including 11 homozygotes (gnomAD). The observed variant frequency within African or African-American control individuals in the gnomAD database is well above the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.371+17G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have 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 benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811999 SCV001472955 benign not provided 2020-03-18 criteria provided, single submitter clinical testing
Invitae RCV002055446 SCV002427336 benign Long QT syndrome 2024-01-31 criteria provided, single submitter clinical testing

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