rs369338222
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_006231.4(POLE):c.3670G>T(p.Ala1224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006231.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251354Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135892
GnomAD4 exome AF: 0.000183 AC: 267AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 127AN XY: 727238
GnomAD4 genome AF: 0.000105 AC: 16AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74364
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 15, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 17, 2024 | 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. - |
Colorectal cancer, susceptibility to, 12 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Dec 04, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at