ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.1758-11C>G (rs145554982)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000300502 SCV000411571 uncertain significance Congenital nephrotic syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Integrated Genetics/Laboratory Corporation of America RCV000590107 SCV000698499 benign not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The NPHS1 c.1758-11C>G variant involves the alteration of a non-conserved nucleotide in the intronic region . One in silico tool predicts a benign outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 649/102412 control chromosomes (1 homozygote), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.035667 (160/4486). This frequency is about 9 times the estimated maximal expected allele frequency of a pathogenic NPHS1 variant in Finnish population (0.0039, see calculation in additional comments), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. This variant has been reported in a patient with end stage renal disease who also carries a pathogenic WT1 variant (c.1385G>A/p.Arg462Gln). Although one other clinical diagnostic laboratory classified this variant as uncertain significance, multiple lines of evidence support neutrality of this variant. Therefore, this variant is classified as benign.

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