ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.3147+5G>A

gnomAD frequency: 0.01118  dbSNP: rs74859201
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000117754 SCV000152010 benign not specified 2013-08-15 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000117754 SCV000269427 benign not specified 2015-01-13 criteria provided, single submitter clinical testing c.3147+5G>A in intron 31 of NEB: This variant is not expected to have clinical s ignificance because it has been identified in 1.9% (160/8370) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs74859201).
PreventionGenetics, part of Exact Sciences RCV000117754 SCV000307341 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000117754 SCV000522708 benign not specified 2016-03-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics RCV000117754 SCV000614175 benign not specified 2016-10-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000559782 SCV000640772 benign Nemaline myopathy 2 2024-02-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000559782 SCV001290733 benign Nemaline myopathy 2 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000117754 SCV001363580 benign not specified 2019-04-01 criteria provided, single submitter clinical testing Variant summary: NEB c.3147+5G>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. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes and two predict the variant weakens the 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.016 in 120684 control chromosomes in the ExAC database, including 17 homozygotes. The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in NEB causing Nemaline Myopathy 2 phenotype (0.0035), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3147+5G>A in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics RCV004707975 SCV005238924 benign not provided criteria provided, single submitter not provided
Natera, Inc. RCV000559782 SCV002077756 likely benign Nemaline myopathy 2 2019-11-28 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.