dbSNP rs3136804: POLB:p.Tyr296Tyr (chr8-42369963-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_002690.3(POLB):c.888C>T(p.Tyr296Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

POLB
NM_002690.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.944

Publications

3 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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.086).

BP7

Synonymous conserved (PhyloP=0.944 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3 link	c.888C>T	p.Tyr296Tyr	synonymous_variant	Exon 13 of 14	ENST00000265421.9	NP_002681.1	P06746

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9 link	c.888C>T	p.Tyr296Tyr	synonymous_variant	Exon 13 of 14	1	NM_002690.3	ENSP00000265421.4		P06746

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457248

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108226

Other (OTH)

AF:

0.00

AC:

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.1

(source)

DANN

Benign

0.68

PhyloP100

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over