12-132687330-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_006231.4(POLE):c.-15G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,495,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000067 ( 0 hom. )
Consequence
POLE
NM_006231.4 5_prime_UTR
NM_006231.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0870
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=-0.81).
BP6
?
Variant 12-132687330-C-T is Benign according to our data. Variant chr12-132687330-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.-15G>A | 5_prime_UTR_variant | 1/49 | ENST00000320574.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.-15G>A | 5_prime_UTR_variant | 1/49 | 1 | NM_006231.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000856 AC: 13AN: 151944Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000187 AC: 2AN: 106904Hom.: 0 AF XY: 0.0000337 AC XY: 2AN XY: 59286
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GnomAD4 exome AF: 0.00000670 AC: 9AN: 1343086Hom.: 0 Cov.: 31 AF XY: 0.00000905 AC XY: 6AN XY: 662744
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GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152052Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 08, 2015 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 06, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at