Genetic Variant POLB:c.621+165A>G (chr8-42361530-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.621+165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 611,534 control chromosomes in the GnomAD database, including 17,858 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 0.28 ( 10253 hom., cov: 33)

Exomes 𝑓: 0.15 ( 7605 hom. )

Consequence

POLB
NM_002690.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.241

Publications

11 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002690.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLB	NM_002690.3	MANE Select	c.621+165A>G		intron	N/A	NP_002681.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLB	ENST00000265421.9	TSL:1 MANE Select	c.621+165A>G	intron	N/A	ENSP00000265421.4
POLB	ENST00000519524.1	TSL:5	n.473A>G	non_coding_transcript_exon	Exon 4 of 4
POLB	ENST00000518925.5	TSL:5	c.726+165A>G	intron	N/A	ENSP00000430784.1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42168

AN:

152086

Hom.:

10207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.227

GnomAD4 exome

AF:

0.150

AC:

68673

AN:

459330

Hom.:

7605

Cov.:

AF XY:

0.151

AC XY:

36787

AN XY:

244250

show subpopulations

African (AFR)

AF:

0.664

AC:

8496

AN:

12804

American (AMR)

AF:

0.112

AC:

2264

AN:

20190

Ashkenazi Jewish (ASJ)

AF:

0.0874

AC:

1245

AN:

14242

East Asian (EAS)

AF:

0.158

AC:

4869

AN:

30838

South Asian (SAS)

AF:

0.239

AC:

11104

AN:

46470

European-Finnish (FIN)

AF:

0.167

AC:

5161

AN:

30970

Middle Eastern (MID)

AF:

0.150

AC:

408

AN:

2716

European-Non Finnish (NFE)

AF:

0.112

AC:

30653

AN:

274734

Other (OTH)

AF:

0.170

AC:

4473

AN:

26366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2541

5081

7622

10162

12703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.278

AC:

42262

AN:

152204

Hom.:

10253

Cov.:

AF XY:

0.277

AC XY:

20623

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.662

AC:

27460

AN:

41496

American (AMR)

AF:

0.151

AC:

2305

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0844

AC:

293

AN:

3472

East Asian (EAS)

AF:

0.148

AC:

769

AN:

5180

South Asian (SAS)

AF:

0.254

AC:

1225

AN:

4824

European-Finnish (FIN)

AF:

0.188

AC:

1996

AN:

10600

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7627

AN:

68010

Other (OTH)

AF:

0.228

AC:

482

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1131

2261

3392

4522

5653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.170

Hom.:

1477

Bravo

AF:

0.287

Asia WGS

AF:

0.296

AC:

1030

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.0

(source)

DANN

Benign

0.55

PhyloP100

-0.24

PromoterAI

-0.0014

Neutral

(source)

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over