ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1488A>T (p.Thr496=) (rs9282599)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084609 SCV000166015 benign Familial adenomatous polyposis 1 2020-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000164173 SCV000214791 likely benign Hereditary cancer-predisposing syndrome 2014-07-24 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.
Illumina Clinical Services Laboratory,Illumina RCV000318991 SCV000451989 likely benign APC-Associated Polyposis Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508123 SCV000600044 likely benign not specified 2016-11-15 criteria provided, single submitter clinical testing
Color Health, Inc RCV000164173 SCV000681468 benign Hereditary cancer-predisposing syndrome 2016-03-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587584 SCV000693998 benign not provided 2017-06-09 criteria provided, single submitter clinical testing Variant summary: The APC c.1488A>T (p.Thr496Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 55/121488 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.006028 (52/8626). This frequency is about 84 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587584 SCV000887507 benign not provided 2018-03-11 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000587584 SCV001746823 likely benign not provided 2021-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000587584 SCV001830129 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356780 SCV001552041 benign Carcinoma of colon no assertion criteria provided clinical testing The APC p.Thr496= variant was identified in 1 of 338 proband chromosomes (frequency: 0.01) from individuals or families with colorectal cancer, and was not identified in 244 control chromosomes from healthy individuals (Chang 2016, Chen 2006). The variant was also identified in dbSNP (ID: rs9282599) as “With Likely benign allele”, ClinVar (classified as benign by Invitae, Color Genomics and Integrated Genetics/Laboratory Corporation of America; as likely benign by Ambry Genetics and Quest Diagnostics Nichols Institute San Juan Capistrano), Clinvitae, LOVD 3.0 (Probably does not affect function), or Zhejiang Colon Cancer Database (2X). The variant was not identified in GeneInsight-COGR, Cosmic, or UMD-LSDB databases. The variant was identified in control databases in 123 of 277014 chromosomes (1 homozygous) at a frequency of 0.0004 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include East Asian in 122 of 18852 chromosomes (freq: 0.01), Finnish in 1 of 25786 chromosomes (freq: 0.00004), while the variant was not observed in the African, Other, Latino, European, Ashkenazi Jewish, and South Asian populations. The p.Thr496= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics,Academic Medical Center RCV000508123 SCV001920993 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000587584 SCV001954828 likely benign not provided no assertion criteria provided clinical testing

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