ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.1035C>T (p.Gly345=)

gnomAD frequency: 0.00038  dbSNP: rs146605798
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000587475 SCV000149684 likely benign not provided 2021-04-28 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25980754)
Ambry Genetics RCV000115775 SCV000214392 likely benign Hereditary cancer-predisposing syndrome 2014-10-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001081028 SCV000252774 benign Microcephaly, normal intelligence and immunodeficiency 2021-12-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587475 SCV000697931 benign not provided 2016-12-16 criteria provided, single submitter clinical testing Variant summary: The NBN c.1035C>T (p.Gly345Gly) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. multiple in silico models predict the formation of a cryptic donor site with a higher score than the canonocal splice donor site, however, these predictions have yet to be confirmed by functional studies. This variant was found in 59/121358 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.0067021 (58/8654). This frequency is about 54 times the estimated maximal expected allele frequency of a pathogenic NBN variant (0.000125), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587475 SCV000889539 likely benign not provided 2020-11-17 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000115775 SCV000902653 likely benign Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001081028 SCV001321725 likely benign Microcephaly, normal intelligence and immunodeficiency 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genetic Services Laboratory,University of Chicago RCV001818276 SCV002069612 uncertain significance not specified 2019-08-27 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000115775 SCV002536565 likely benign Hereditary cancer-predisposing syndrome 2021-11-01 criteria provided, single submitter curation
True Health Diagnostics RCV000115775 SCV000788074 likely benign Hereditary cancer-predisposing syndrome 2017-08-22 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000587475 SCV001553002 uncertain significance not provided no assertion criteria provided clinical testing The NBN p.Gly345Gly variant was not identified in the literature nor was it identified in the Cosmic, LOVD 3.0, Zhejiang Colon Cancer databases. The variant was also identified in the following databases: dbSNP (ID: rs146605798) as “With Likely benign, Uncertain significance allele”, ClinVar (3x, as Benign by Invitae, likely benign by Amby Genetics and uncertain significance by GeneDx), Clinvitae (3x). The variant was identified in control databases in 109 of 277086 chromosomes at a frequency of 0.000393 in the following populations: “other” in 1 of 6466 chromosomes (freq. 0.00015), European in 1 of 126612 chromosomes (freq. 0.000008), East Asian in 104 of 18868 chromosomes (freq. 0.0055), Finnish in 3 of 25794 chromosomes (freq. 0.000116) (Genome Aggregation Consortium Feb 27, 2017). The p.Gly345Gly variant is not expected to have clinical significance because it does not result in a change of amino acid. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as 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.