ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.474C>T (p.Arg158=)

gnomAD frequency: 0.00009  dbSNP: rs139200646
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163158 SCV000213675 likely benign Hereditary cancer-predisposing syndrome 2016-02-18 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 RCV000206827 SCV000259803 likely benign Li-Fraumeni syndrome 2021-12-17 criteria provided, single submitter clinical testing
GeneDx RCV001704160 SCV000523505 likely benign not provided 2020-08-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26205736, 24729566, 20010306, 29958926, 29979965, 32324779, 28861920)
Color Diagnostics, LLC DBA Color Health RCV000163158 SCV000686741 likely benign Hereditary cancer-predisposing syndrome 2016-06-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000424020 SCV000918327 benign not specified 2018-06-15 criteria provided, single submitter clinical testing Variant summary: TP53 c.474C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within African control individuals in the gnomAD database is approximately 11.57 fold of the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Li-Fraumeni Syndrome phenotype (4e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant was also found in 2/9884 individuals who are cancer-free and older than age 70, suggesting this variant is unlikely to be pathogenic. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genetic Services Laboratory,University of Chicago RCV000424020 SCV002069584 likely benign not specified 2019-08-09 criteria provided, single submitter clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State RCV002225476 SCV002505075 benign Hereditary breast ovarian cancer syndrome 2022-04-19 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000163158 SCV002530463 benign Hereditary cancer-predisposing syndrome 2020-11-11 criteria provided, single submitter curation
Genome-Nilou Lab RCV000163158 SCV002582586 likely benign Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002288716 SCV002582887 likely benign Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing

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