ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1125-3C>T (rs587781326)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129069 SCV000183770 likely benign Hereditary cancer-predisposing syndrome 2020-05-29 criteria provided, single submitter clinical testing In silico models in agreement (benign);RNA Studies
Illumina Clinical Services Laboratory,Illumina RCV000361912 SCV000475296 uncertain significance Microcephaly, normal intelligence and immunodeficiency 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.
GeneDx RCV000445205 SCV000527317 likely benign not specified 2018-01-31 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.
Invitae RCV000361912 SCV000553068 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-07-30 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the NBN gene. It does not directly change the encoded amino acid sequence of the NBN protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 140859). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.
Color Health, Inc RCV000129069 SCV000909713 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-01 criteria provided, single submitter clinical testing

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