ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4533C>T (p.Leu1511=)

gnomAD frequency: 0.00007  dbSNP: rs150089434
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004563240 SCV000282757 likely benign Familial adenomatous polyposis 1 2025-02-03 criteria provided, single submitter clinical testing
GeneDx RCV001705237 SCV000516191 likely benign not provided 2021-03-08 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26010451)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001705237 SCV000600103 likely benign not provided 2023-03-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000568570 SCV000667297 likely benign Hereditary cancer-predisposing syndrome 2015-01-22 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.
Color Diagnostics, LLC DBA Color Health RCV000568570 SCV000681671 likely benign Hereditary cancer-predisposing syndrome 2017-01-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000418393 SCV000694055 likely benign not specified 2019-05-23 criteria provided, single submitter clinical testing Variant summary: APC c.4533C>T alters a non-conserved nucleotide resulting 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 variant allele was found at a frequency of 4.8e-05 in 250356 control chromosomes, predominantly within the Non-Finnish European subpopulation at a frequency of 7.1e-05 in the gnomAD database. The observed variant frequency in the Non-Finnish European subpopulation is approximately the same as the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis (FAP) phenotype (7.1e-05), suggesting that the variant is benign. In addition, the variant occurs in the North-western European subpopulation with an even higher frequency (i.e. 0.00012) further supporting a benign role. To our knowledge, no occurrence of c.4533C>T in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Five other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all of them classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Sema4, Sema4 RCV000568570 SCV002534351 likely benign Hereditary cancer-predisposing syndrome 2021-06-28 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000418393 SCV004025064 likely benign not specified 2025-03-04 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998670 SCV004837946 likely benign Classic or attenuated familial adenomatous polyposis 2024-02-05 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004563240 SCV004931821 benign Familial adenomatous polyposis 1 2024-03-27 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV004563240 SCV005880652 benign Familial adenomatous polyposis 1 2025-02-01 criteria provided, single submitter clinical testing

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