chr12-132649802-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1224L) has been classified as Uncertain significance.
Frequency
Consequence
NM_006231.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.3670G>T | p.Ala1224Ser | missense_variant | 30/49 | ENST00000320574.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.3670G>T | p.Ala1224Ser | missense_variant | 30/49 | 1 | NM_006231.4 | P1 |
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
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 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 15, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at