rs12678588
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002690.3(POLB):c.410G>A(p.Arg137Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000327 in 1,591,400 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00053 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 3 hom. )
Consequence
POLB
NM_002690.3 missense
NM_002690.3 missense
Scores
4
15
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.17
Genes affected
POLB (HGNC:9174): (DNA polymerase beta) The protein encoded by this gene is a DNA polymerase involved in base excision and repair, also called gap-filling DNA synthesis. The encoded protein, acting as a monomer, is normally found in the cytoplasm, but it translocates to the nucleus upon DNA damage. Several transcript variants of this gene exist, but the full-length nature of only one has been described to date. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009117395).
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLB | NM_002690.3 | c.410G>A | p.Arg137Gln | missense_variant | 7/14 | ENST00000265421.9 | NP_002681.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLB | ENST00000265421.9 | c.410G>A | p.Arg137Gln | missense_variant | 7/14 | 1 | NM_002690.3 | ENSP00000265421 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000533 AC: 81AN: 152094Hom.: 3 Cov.: 32
GnomAD3 genomes
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32
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GnomAD3 exomes AF: 0.00138 AC: 345AN: 250346Hom.: 1 AF XY: 0.00110 AC XY: 149AN XY: 135422
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GnomAD4 exome AF: 0.000305 AC: 439AN: 1439188Hom.: 3 Cov.: 24 AF XY: 0.000275 AC XY: 197AN XY: 717542
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GnomAD4 genome AF: 0.000532 AC: 81AN: 152212Hom.: 3 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74406
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.010
.;B;.
Vest4
0.21
MVP
MPC
0.75
ClinPred
T
GERP RS
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gMVP
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