ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.1930+10C>T (rs76131336)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000253090 SCV000310562 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000302690 SCV000411565 uncertain significance Congenital nephrotic syndrome 2018-01-13 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.
Athena Diagnostics Inc RCV000712422 SCV000842915 benign not provided 2018-07-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000253090 SCV000919899 benign not specified 2018-10-01 criteria provided, single submitter clinical testing Variant summary: NPHS1 c.1930+10C>T 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 0.0093 in 276940 control chromosomes in the gnomAD database, including 27 homozygotes. The observed variant frequency is approximately 2.78 fold of 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 benign. To our knowledge, no occurrence of c.1930+10C>T in individuals affected with Nephrotic Syndrome, Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000712422 SCV001113810 benign not provided 2019-12-31 criteria provided, single submitter clinical testing

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