chr12-132632794-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_006231.4(POLE):c.6006G>A(p.Ala2002Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,603,298 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006231.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6006G>A | p.Ala2002Ala | splice_region_variant, synonymous_variant | 44/49 | ENST00000320574.10 | NP_006222.2 | |
POLE | XM_011534795.4 | c.6006G>A | p.Ala2002Ala | splice_region_variant, synonymous_variant | 44/48 | XP_011533097.1 | ||
POLE | XM_011534797.4 | c.5085G>A | p.Ala1695Ala | splice_region_variant, synonymous_variant | 36/40 | XP_011533099.1 | ||
POLE | XM_011534802.4 | c.2994G>A | p.Ala998Ala | splice_region_variant, synonymous_variant | 20/24 | XP_011533104.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000209 AC: 50AN: 239638Hom.: 0 AF XY: 0.000214 AC XY: 28AN XY: 130730
GnomAD4 exome AF: 0.000105 AC: 152AN: 1451100Hom.: 1 Cov.: 32 AF XY: 0.000125 AC XY: 90AN XY: 721704
GnomAD4 genome AF: 0.000184 AC: 28AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74356
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2021 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 02, 2025 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | POLE: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Mar 04, 2025 | - - |
Colorectal cancer, susceptibility to, 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 01, 2015 | 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