Variant chr8-42369287-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002690.3(POLB):c.725C>G(p.Pro242Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0152 in 1,581,432 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 32)

Exomes 𝑓: 0.016 ( 244 hom. )

Consequence

POLB
NM_002690.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.48

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]

POLB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059150755).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1600/152136) while in subpopulation NFE AF= 0.0182 (1234/67988). AF 95% confidence interval is 0.0173. There are 12 homozygotes in gnomad4. There are 723 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLB	NM_002690.3 linkuse as main transcript	c.725C>G	p.Pro242Arg	missense_variant	12/14	ENST00000265421.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLB	ENST00000265421.9 linkuse as main transcript	c.725C>G	p.Pro242Arg	missense_variant	12/14	1	NM_002690.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1600

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0106

AC:

2618

AN:

247430

Hom.:

AF XY:

0.0103

AC XY:

1378

AN XY:

133960

show subpopulations

Gnomad AFR exome

AF:

0.00208

Gnomad AMR exome

AF:

0.00357

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00412

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0156

AC:

22359

AN:

1429296

Hom.:

244

Cov.:

AF XY:

0.0154

AC XY:

11011

AN XY:

713068

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00396

Gnomad4 ASJ exome

AF:

0.00282

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.00392

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0187

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.0105

AC:

1600

AN:

152136

Hom.:

Cov.:

AF XY:

0.00972

AC XY:

723

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00275

Gnomad4 AMR

AF:

0.00642

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.00987

TwinsUK

AF:

0.0197

AC:

ALSPAC

AF:

0.0221

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0151

AC:

130

ExAC

AF:

0.0111

AC:

1341

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0154

EpiControl

AF:

0.0144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

T;T

Eigen

Benign

0.087

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.12

Sift

Benign

0.063

T;D

Sift4G

Benign

0.22

T;D

Polyphen

0.0

B;.

Vest4

0.18

MPC

0.68

ClinPred

0.039

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over