ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.2971G>C (p.Val991Leu) (rs34736717)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000242230 SCV000310571 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000330167 SCV000411557 likely benign Congenital nephrotic syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Integrated Genetics/Laboratory Corporation of America RCV000242230 SCV000917908 benign not specified 2018-04-20 criteria provided, single submitter clinical testing Variant summary: NPHS1 c.2971G>C (p.Val991Leu) results in a conservative amino acid change located in the Fibronectin type III domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.013 in 277180 control chromosomes, predominantly within the African subpopulation at a frequency of 0.14 in the gnomAD database, including 231 homozygotes. The observed variant frequency within African control individuals is approximately 42 fold above the estimated maximal expected allele frequency for a pathogenic variant in NPHS1 causing Nephrotic Syndrome, Type 1 phenotype (0.0034), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant has been cited in the literature as a polymorphism (e.g., Machuca_2010). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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