ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7190-33TTGT[7] (rs149197458)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000679407 SCV000806309 likely benign not provided 2016-08-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001194092 SCV001363366 uncertain significance not specified 2019-10-10 criteria provided, single submitter clinical testing Variant summary: NF1 c.7127-11_7127-8dupGTTT 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 0.001 in 154686 control chromosomes, predominantly at a frequency of 0.0053 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 25 fold of the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Neurofibromatosis Type 1 phenotype (0.00021), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.7127-11_7127-8dupGTTT has been reported in the literature in a proband and mother affected with Neurofibromatosis Type 1 (Tsipi_2018). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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