Genetic Variant POLB:c.-196G>T (chr8-42338429-G-T) – 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.-196G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 399,750 control chromosomes in the GnomAD database, including 5,597 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 0.15 ( 3598 hom., cov: 32)

Exomes 𝑓: 0.10 ( 1999 hom. )

Consequence

POLB
NM_002690.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.417

Publications

7 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:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLB	NM_002690.3	MANE Select	c.-196G>T		upstream_gene	N/A	NP_002681.1	P06746

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POLB	ENST00000265421.9	TSL:1 MANE Select	c.-196G>T	upstream_gene	N/A	ENSP00000265421.4	P06746
POLB	ENST00000929417.1		c.-196G>T	upstream_gene	N/A	ENSP00000599476.1
POLB	ENST00000518925.5	TSL:5	c.-196G>T	upstream_gene	N/A	ENSP00000430784.1	E7EW18

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

22932

AN:

148156

Hom.:

3585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.0322

Gnomad AMR

AF:

0.0687

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0333

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.103

AC:

25958

AN:

251458

Hom.:

1999

Cov.:

AF XY:

0.109

AC XY:

15058

AN XY:

138156

show subpopulations

African (AFR)

AF:

0.432

AC:

3611

AN:

8362

American (AMR)

AF:

0.0606

AC:

811

AN:

13374

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

196

AN:

5536

East Asian (EAS)

AF:

0.198

AC:

2831

AN:

14322

South Asian (SAS)

AF:

0.194

AC:

8706

AN:

44890

European-Finnish (FIN)

AF:

0.126

AC:

1921

AN:

15288

Middle Eastern (MID)

AF:

0.0917

AC:

AN:

872

European-Non Finnish (NFE)

AF:

0.0474

AC:

6448

AN:

136108

Other (OTH)

AF:

0.107

AC:

1354

AN:

12706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

911

1821

2732

3642

4553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<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:

0.155

AC:

22984

AN:

148292

Hom.:

3598

Cov.:

AF XY:

0.160

AC XY:

11581

AN XY:

72412

show subpopulations

African (AFR)

AF:

0.403

AC:

16478

AN:

40888

American (AMR)

AF:

0.0686

AC:

1019

AN:

14862

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

AN:

3434

East Asian (EAS)

AF:

0.150

AC:

708

AN:

4734

South Asian (SAS)

AF:

0.210

AC:

942

AN:

4480

European-Finnish (FIN)

AF:

0.125

AC:

1214

AN:

9744

Middle Eastern (MID)

AF:

0.0514

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0333

AC:

2227

AN:

66910

Other (OTH)

AF:

0.136

AC:

283

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

736

1471

2207

2942

3678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.0471

Hom.:

188

Bravo

AF:

0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.9

(source)

DANN

Benign

0.93

PhyloP100

-0.42

PromoterAI

0.018

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over