rs564807391
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_006231.4(POLE):c.4291-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,862 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000044 ( 1 hom. )
Consequence
POLE
NM_006231.4 splice_polypyrimidine_tract, intron
NM_006231.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001350
2
Clinical Significance
Conservation
PhyloP100: 0.519
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 12-132643572-G-A is Benign according to our data. Variant chr12-132643572-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 514373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132643572-G-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.4291-12C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000320574.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.4291-12C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000798 AC: 20AN: 250660Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135508
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GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461534Hom.: 1 Cov.: 36 AF XY: 0.0000550 AC XY: 40AN XY: 727054
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152328Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4AN XY: 74508
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 24, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 05, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at