ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1814+3A>G

gnomAD frequency: 0.00003  dbSNP: rs376886420
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000238879 SCV000296904 uncertain significance Retinoblastoma 2015-10-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000238879 SCV000551819 likely benign Retinoblastoma 2023-12-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV001013283 SCV001173851 likely benign Hereditary cancer-predisposing syndrome 2021-07-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
All of Us Research Program, National Institutes of Health RCV000238879 SCV004815127 uncertain significance Retinoblastoma 2024-01-11 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +3 position of intron 18 of the RB1 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing, although this prediction has not been confirmed in published RNA studies. This variant has not been reported in individuals affected with RB1-related disorders in the literature. However a different variant at this position has been observed in a patient affected with bilateral retinoblastoma (c.1814+3A>C; PMID: 32218800) and has been classified as pathogenic in ClinVar (Variation ID: VCV000237664). This variant has been identified in 6/249688 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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