ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.474C>T (p.Arg158=) (rs139200646)

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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 RCV000163158 SCV000213675 likely benign Hereditary cancer-predisposing syndrome 2016-02-18 criteria provided, single submitter clinical testing
Invitae RCV000206827 SCV000259803 likely benign not provided 2019-01-21 criteria provided, single submitter clinical testing
GeneDx RCV000424020 SCV000523505 likely benign not specified 2017-10-10 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.
Color RCV000163158 SCV000686741 likely benign Hereditary cancer-predisposing syndrome 2016-06-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.

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