rs375256819
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_006231.4(POLE):c.6507G>T(p.Leu2169Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006231.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6507G>T | p.Leu2169Leu | synonymous_variant | Exon 46 of 49 | ENST00000320574.10 | NP_006222.2 | |
POLE | XM_011534795.4 | c.6507G>T | p.Leu2169Leu | synonymous_variant | Exon 46 of 48 | XP_011533097.1 | ||
POLE | XM_011534797.4 | c.5586G>T | p.Leu1862Leu | synonymous_variant | Exon 38 of 40 | XP_011533099.1 | ||
POLE | XM_011534802.4 | c.3495G>T | p.Leu1165Leu | synonymous_variant | Exon 22 of 24 | XP_011533104.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1453654Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 722464
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Benign:1
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Hereditary cancer-predisposing syndrome Benign:1
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