ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4893T>C (p.Ser1631=) (rs35634377)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001083248 SCV000153822 benign Familial adenomatous polyposis 1 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000211917 SCV000167010 benign not specified 2014-04-08 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.
Ambry Genetics RCV000123668 SCV000213278 likely benign Hereditary cancer-predisposing syndrome 2014-08-01 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 RCV000388181 SCV000452016 likely benign APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000211917 SCV000600106 likely benign not specified 2016-07-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000123668 SCV000681693 benign Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586060 SCV000694060 benign not provided 2016-01-25 criteria provided, single submitter clinical testing Variant summary: Variant affects a non-conserved nucleotide and results in a synonymous mutation. Mutation taster predicts disease causing impact while 5/5 in silico tools via Alamut predict no significant effect on normal splicing. It was predominantly observed in the African subcohort of the ExAC project at an allele frequency of 0.538% which exeeds the maximal expected allele frequency of a disease causing APC allele 0.006% indicating a neutral impact. Additionally, clinical diagnostic centers classify variant as Likely Bening/Benign via ClinVar (without evidence to independently evaluate). Considering all evidence, the variant was classified as Benign.
PreventionGenetics,PreventionGenetics RCV000211917 SCV000805415 benign not specified 2017-06-09 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586060 SCV000887525 benign not provided 2017-09-27 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357649 SCV001553177 likely benign Carcinoma of colon no assertion criteria provided clinical testing The APC p.Ser1631= variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs35634377) as "With other allele", and in ClinVar (classified as benign by Invitae, GeneDx, Color and three other submitters; and as likely benign by Ambry Genetics and two other submitters). The variant was identified in control databases in 211 of 276950 chromosomes at a frequency of 0.0008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 190 of 24022 chromosomes (freq: 0.008, increasing the likelihood this could be a low frequency benign variant), Other in 4 of 6460 chromosomes (freq: 0.0006), Latino in 16 of 34412 chromosomes (freq: 0.0005), and European in 1 of 126492 chromosomes (freq: 0.000008), while the variant was not observed in the Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Ser1631= 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) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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