dbSNP rs3136794: POLB:c.709-235A>G (chr8-42369036-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002690.3(POLB):c.709-235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 333,096 control chromosomes in the GnomAD database, including 12,544 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.

Frequency

Genomes: 𝑓 0.27 ( 9771 hom., cov: 32)

Exomes 𝑓: 0.14 ( 2773 hom. )

Consequence

POLB
NM_002690.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.105

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3 link	c.709-235A>G		intron_variant	Intron 11 of 13	ENST00000265421.9	NP_002681.1	P06746

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9 link	c.709-235A>G		intron_variant	Intron 11 of 13	1	NM_002690.3	ENSP00000265421.4		P06746

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41372

AN:

151958

Hom.:

9724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0845

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.143

AC:

25947

AN:

181020

Hom.:

2773

Cov.:

AF XY:

0.141

AC XY:

13111

AN XY:

92864

show subpopulations

African (AFR)

AF:

0.638

AC:

3412

AN:

5350

American (AMR)

AF:

0.132

AC:

701

AN:

5308

Ashkenazi Jewish (ASJ)

AF:

0.0871

AC:

593

AN:

6812

East Asian (EAS)

AF:

0.160

AC:

2514

AN:

15692

South Asian (SAS)

AF:

0.249

AC:

1499

AN:

6020

European-Finnish (FIN)

AF:

0.169

AC:

2213

AN:

13122

Middle Eastern (MID)

AF:

0.160

AC:

147

AN:

916

European-Non Finnish (NFE)

AF:

0.110

AC:

12789

AN:

115788

Other (OTH)

AF:

0.173

AC:

2079

AN:

12012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

986

1971

2957

3942

4928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.273

AC:

41468

AN:

152076

Hom.:

9771

Cov.:

AF XY:

0.272

AC XY:

20262

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.645

AC:

26739

AN:

41462

American (AMR)

AF:

0.150

AC:

2289

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0845

AC:

293

AN:

3468

East Asian (EAS)

AF:

0.147

AC:

763

AN:

5178

South Asian (SAS)

AF:

0.254

AC:

1223

AN:

4824

European-Finnish (FIN)

AF:

0.188

AC:

1987

AN:

10566

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7593

AN:

67968

Other (OTH)

AF:

0.226

AC:

477

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1121

2242

3364

4485

5606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0935

Hom.:

241

Bravo

AF:

0.281

Asia WGS

AF:

0.295

AC:

1027

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.1

(source)

DANN

Benign

0.66

PhyloP100

-0.10

PromoterAI

0.021

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over