rs12678588

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

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.17
Variant links:
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]

Genome browser will be placed here

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
POLBNM_002690.3 linkuse as main transcriptc.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
POLBENST00000265421.9 linkuse as main transcriptc.410G>A p.Arg137Gln missense_variant 7/141 NM_002690.3 ENSP00000265421 P1

Frequencies

GnomAD3 genomes
AF:
0.000533
AC:
81
AN:
152094
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00242
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00616
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00138
AC:
345
AN:
250346
Hom.:
1
AF XY:
0.00110
AC XY:
149
AN XY:
135422
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00704
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00524
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.000655
GnomAD4 exome
AF:
0.000305
AC:
439
AN:
1439188
Hom.:
3
Cov.:
24
AF XY:
0.000275
AC XY:
197
AN XY:
717542
show subpopulations
Gnomad4 AFR exome
AF:
0.000212
Gnomad4 AMR exome
AF:
0.00623
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00321
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000101
Gnomad4 OTH exome
AF:
0.000252
GnomAD4 genome
AF:
0.000532
AC:
81
AN:
152212
Hom.:
3
Cov.:
32
AF XY:
0.000524
AC XY:
39
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00242
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00618
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000219
Hom.:
0
Bravo
AF:
0.000774
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00117
AC:
142
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
.;T;T
Eigen
Benign
-0.21
Eigen_PC
Benign
0.040
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.0091
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.49
.;N;.
MutationTaster
Benign
0.98
D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.080
N;N;N
REVEL
Benign
0.047
Sift
Benign
0.20
T;T;T
Sift4G
Benign
0.50
T;T;T
Polyphen
0.010
.;B;.
Vest4
0.21
MVP
0.32
MPC
0.75
ClinPred
0.017
T
GERP RS
5.3
Varity_R
0.30
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12678588; hg19: chr8-42213073; API