ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.37+5G>A (rs116735828)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129181 SCV000183916 benign Hereditary cancer-predisposing syndrome 2014-12-02 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae RCV000988092 SCV000262314 benign Microcephaly, normal intelligence and immunodeficiency 2020-12-04 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000389618 SCV000332541 benign not specified 2015-06-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129181 SCV000685778 benign Hereditary cancer-predisposing syndrome 2015-04-03 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000389618 SCV000806437 benign not specified 2017-01-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759176 SCV000888338 benign not provided 2018-08-27 criteria provided, single submitter clinical testing
Mendelics RCV000988092 SCV001137672 benign Microcephaly, normal intelligence and immunodeficiency 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282951 SCV001157388 benign none provided 2020-04-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000988092 SCV001327165 benign Microcephaly, normal intelligence and immunodeficiency 2017-05-01 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneDx RCV000759176 SCV001865616 benign not provided 2018-11-30 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30306255, 25980754, 25318351, 24549055)
True Health Diagnostics RCV000129181 SCV000788079 likely benign Hereditary cancer-predisposing syndrome 2018-01-05 no assertion criteria provided clinical testing
Natera, Inc. RCV000988092 SCV001457059 benign Microcephaly, normal intelligence and immunodeficiency 2020-06-11 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354386 SCV001548992 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The NBN c.37+5G>A variant was identified in 4 of 1626 proband chromosomes (frequency: 0.002) from individuals or families with breast and ovarian cancer (Castera 2014, Yorczyk 2015). The variant was also identified in dbSNP (ID: rs116735828) as With Benign allele, ClinVar (classified as benign by Ambry Genetics, Invitae), Clinvitae (classified as benign by ClinVar, Invitae), LOVD 3.0, databases. The variant was identified in control databases in 755(12 homozygous) of 272168 chromosomes at a frequency of 0.003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 549 of 23426 chromosomes (freq: 0.023). The c.37+5G>A variant is located in the 5' splice region but does not affect the invariant +1 and +2 positions. However, positions +3 to +6 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition, 4 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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