rs201587262
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_006231.4(POLE):c.5173+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,521,366 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 2 hom. )
Consequence
POLE
NM_006231.4 intron
NM_006231.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.10
Genes affected
POLE (HGNC:9177): (DNA polymerase epsilon, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 12-132642159-G-A is Benign according to our data. Variant chr12-132642159-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 380433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132642159-G-A is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.5173+18C>T | intron_variant | ENST00000320574.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.5173+18C>T | intron_variant | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000161 AC: 31AN: 192732Hom.: 1 AF XY: 0.000167 AC XY: 17AN XY: 101804
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GnomAD4 exome AF: 0.000288 AC: 394AN: 1369052Hom.: 2 Cov.: 31 AF XY: 0.000251 AC XY: 169AN XY: 672974
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 22, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 23, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at