chr12-132625671-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_006231.4(POLE):c.6631C>T(p.Leu2211=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000093 in 1,613,636 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L2211L) has been classified as Likely benign.
Frequency
Consequence
NM_006231.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6631C>T | p.Leu2211= | synonymous_variant | 47/49 | ENST00000320574.10 | |
POLE | XM_011534795.4 | c.6631C>T | p.Leu2211= | synonymous_variant | 47/48 | ||
POLE | XM_011534797.4 | c.5710C>T | p.Leu1904= | synonymous_variant | 39/40 | ||
POLE | XM_011534802.4 | c.3619C>T | p.Leu1207= | synonymous_variant | 23/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.6631C>T | p.Leu2211= | synonymous_variant | 47/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251062Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135724
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461382Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727008
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74386
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 12, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 01, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 04, 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