chr12-132626141-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_006231.4(POLE):c.6507G>A(p.Leu2169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,605,876 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L2169L) has been classified as Likely benign.
Frequency
Consequence
NM_006231.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6507G>A | p.Leu2169= | synonymous_variant | 46/49 | ENST00000320574.10 | |
POLE | XM_011534795.4 | c.6507G>A | p.Leu2169= | synonymous_variant | 46/48 | ||
POLE | XM_011534797.4 | c.5586G>A | p.Leu1862= | synonymous_variant | 38/40 | ||
POLE | XM_011534802.4 | c.3495G>A | p.Leu1165= | synonymous_variant | 22/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.6507G>A | p.Leu2169= | synonymous_variant | 46/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000211 AC: 5AN: 236932Hom.: 0 AF XY: 0.0000234 AC XY: 3AN XY: 128166
GnomAD4 exome AF: 0.0000358 AC: 52AN: 1453654Hom.: 0 Cov.: 32 AF XY: 0.0000318 AC XY: 23AN XY: 722464
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 22, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 02, 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