ClinVar Miner

Submissions for variant NM_002880.4(RAF1):c.1371-15C>A

gnomAD frequency: 0.00006  dbSNP: rs371491379
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Total submissions: 2
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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 RCV001280606 SCV001467820 benign not specified 2020-12-07 criteria provided, single submitter clinical testing Variant summary: RAF1 c.1371-15C>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. 4/4 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 6.6e-05 in 150838 control chromosomes (gnomAD v3 genomes dataset). The observed variant frequency is approximately 2.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in RAF1 causing Noonan Syndrome phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1371-15C>A in individuals affected with Noonan Syndrome 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002069495 SCV002425981 likely benign RASopathy 2023-12-22 criteria provided, single submitter clinical testing

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