Genetic Variant POLB:c.62-89C>T (chr8-42338923-C-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.62-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,198,058 control chromosomes in the GnomAD database, including 435,754 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 0.72 ( 44090 hom., cov: 31)

Exomes 𝑓: 0.86 ( 391664 hom. )

Consequence

POLB
NM_002690.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Publications

19 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 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.62-89C>T		intron	N/A	NP_002681.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLB	ENST00000265421.9	TSL:1 MANE Select	c.62-89C>T	intron	N/A	ENSP00000265421.4
POLB	ENST00000518925.5	TSL:5	c.62-89C>T	intron	N/A	ENSP00000430784.1
POLB	ENST00000520008.5	TSL:2	c.-344+238C>T	intron	N/A	ENSP00000430610.1

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109900

AN:

151950

Hom.:

44079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.938

Gnomad AMR

AF:

0.849

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.853

Gnomad SAS

AF:

0.744

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.888

Gnomad OTH

AF:

0.774

GnomAD4 exome

AF:

0.860

AC:

899404

AN:

1045990

Hom.:

391664

AF XY:

0.859

AC XY:

461966

AN XY:

538048

show subpopulations

African (AFR)

AF:

0.326

AC:

8247

AN:

25274

American (AMR)

AF:

0.904

AC:

38477

AN:

42570

Ashkenazi Jewish (ASJ)

AF:

0.913

AC:

21297

AN:

23322

East Asian (EAS)

AF:

0.850

AC:

32063

AN:

37712

South Asian (SAS)

AF:

0.759

AC:

58143

AN:

76580

European-Finnish (FIN)

AF:

0.831

AC:

43834

AN:

52752

Middle Eastern (MID)

AF:

0.848

AC:

4283

AN:

5050

European-Non Finnish (NFE)

AF:

0.889

AC:

654243

AN:

736116

Other (OTH)

AF:

0.833

AC:

38817

AN:

46614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6163

12326

18488

24651

30814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11536

23072

34608

46144

57680

<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:

0.723

AC:

109924

AN:

152068

Hom.:

44090

Cov.:

AF XY:

0.723

AC XY:

53762

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.340

AC:

14076

AN:

41454

American (AMR)

AF:

0.849

AC:

12976

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.916

AC:

3177

AN:

3470

East Asian (EAS)

AF:

0.853

AC:

4386

AN:

5142

South Asian (SAS)

AF:

0.746

AC:

3600

AN:

4826

European-Finnish (FIN)

AF:

0.812

AC:

8588

AN:

10576

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.888

AC:

60389

AN:

68004

Other (OTH)

AF:

0.773

AC:

1631

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1124

2248

3371

4495

5619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.805

Hom.:

19634

Bravo

AF:

0.713

Asia WGS

AF:

0.705

AC:

2450

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.5

(source)

DANN

Benign

0.68

PhyloP100

-0.11

PromoterAI

0.013

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

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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