rs201249963
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_006231.4(POLE):c.3054C>T(p.Tyr1018Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,609,066 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_006231.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000811 AC: 20AN: 246658Hom.: 0 AF XY: 0.0000900 AC XY: 12AN XY: 133356
GnomAD4 exome AF: 0.0000590 AC: 86AN: 1456946Hom.: 0 Cov.: 30 AF XY: 0.0000524 AC XY: 38AN XY: 724550
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74316
ClinVar
Submissions by phenotype
not provided Benign:3
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Colorectal cancer, susceptibility to, 12 Benign:1
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POLE-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Hereditary cancer-predisposing syndrome Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at