5-112801338-T-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000038.6(APC):c.789T>A(p.Gly263Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000682 in 1,612,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000038.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251146Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135716
GnomAD4 exome AF: 0.0000691 AC: 101AN: 1460690Hom.: 0 Cov.: 30 AF XY: 0.0000495 AC XY: 36AN XY: 726644
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74318
ClinVar
Submissions by phenotype
not provided Benign:4
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The p.Gly263Gly 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. The variant was identified in the ClinVar database (classified as “likely benign” by Ambry Genetics), and in the Exome Aggregation Consortium (ExAC) database where it was present at a very low frequency in a population of European individuals (4/66322 chromosomes, or frequency of 0.00006). The variant was not identified in the literature, nor was it identified in any of the following databases: dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), COSMIC, InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, GeneInsight COGR database, and UMD. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict the creation of a cryptic splice site. 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 predicted benign. -
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Familial adenomatous polyposis 1 Benign:3
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This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
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Hereditary cancer-predisposing syndrome Benign:2
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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. -
not specified Benign:1
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Classic or attenuated familial adenomatous polyposis Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at