12-132661167-GA-G
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_006231.4(POLE):c.2865-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 134,162 control chromosomes in the GnomAD database, including 209 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.043 ( 209 hom., cov: 31)
Exomes 𝑓: 0.21 ( 106 hom. )
Failed GnomAD Quality Control
Consequence
POLE
NM_006231.4 splice_region, intron
NM_006231.4 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.191
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 -16 ACMG points.
BP6
Variant 12-132661167-GA-G is Benign according to our data. Variant chr12-132661167-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 695292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132661167-GA-G is described in Lovd as [Benign]. Variant chr12-132661167-GA-G is described in Lovd as [Likely_benign]. Variant chr12-132661167-GA-G is described in Lovd as [Likely_benign]. Variant chr12-132661167-GA-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.2865-4delT | splice_region_variant, intron_variant | ENST00000320574.10 | NP_006222.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.2865-4delT | splice_region_variant, intron_variant | 1 | NM_006231.4 | ENSP00000322570.5 |
Frequencies
GnomAD3 genomes AF: 0.0425 AC: 5696AN: 134136Hom.: 202 Cov.: 31
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.213 AC: 212152AN: 996606Hom.: 106 Cov.: 0 AF XY: 0.215 AC XY: 106028AN XY: 493402
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Data not reliable, filtered out with message: InbreedingCoeff
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GnomAD4 genome AF: 0.0425 AC: 5708AN: 134162Hom.: 209 Cov.: 31 AF XY: 0.0447 AC XY: 2886AN XY: 64570
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 13, 2019 | - - |
Colorectal cancer, susceptibility to, 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2019 | - - |
Colorectal cancer, susceptibility to, 12;C3554576:Facial dysmorphism-immunodeficiency-livedo-short stature syndrome;C5193036:Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 17, 2022 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at