rs1555221482
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_006231.4(POLE):c.5809C>T(p.Leu1937=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L1937L) has been classified as Uncertain significance.
Frequency
Consequence
NM_006231.4 splice_region, 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.5809C>T | p.Leu1937= | splice_region_variant, synonymous_variant | 42/49 | ENST00000320574.10 | |
POLE | XM_011534795.4 | c.5809C>T | p.Leu1937= | splice_region_variant, synonymous_variant | 42/48 | ||
POLE | XM_011534797.4 | c.4888C>T | p.Leu1630= | splice_region_variant, synonymous_variant | 34/40 | ||
POLE | XM_011534802.4 | c.2797C>T | p.Leu933= | splice_region_variant, synonymous_variant | 18/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.5809C>T | p.Leu1937= | splice_region_variant, synonymous_variant | 42/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459566Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 725922
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Colorectal cancer, susceptibility to, 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 26, 2022 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 05, 2016 | 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