ClinVar Miner

Submissions for variant NM_006393.3(NEBL):c.903+1G>T

gnomAD frequency: 0.00003  dbSNP: rs775057540
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017515 SCV000272206 uncertain significance not provided 2023-02-06 criteria provided, single submitter clinical testing The c.903+1G>T variant in NEBL has been identified in 1 individual with dilated cardiomyopathy (DCM; LMM data) and has also been reported in ClinVar (Variation ID 229050). It has been identified in 0.017% (7/41444) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. While splice and other loss of function variants in NEBL have been reported in individuals with DCM (Purevjav 2010 PMID: 20951326), current evidence is not sufficient to establish with certainty whether loss of function is a disease mechanism for DCM. In summary, despite the predicted severe impact to the protein, the clinical significance of this variant is uncertain, and its frequency suggests that it is unlikely disease causing in the heterozygous state. ACMG/AMP Criteria applied: BS1_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001853471 SCV002149900 uncertain significance Primary dilated cardiomyopathy 2024-01-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the NEBL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NEBL cause disease. This variant is present in population databases (rs775057540, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 229050). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.