rs2976244

Variant names:

• chr8-42349716-T-A
• rs2976244
• NM_002690.3:c.262-291T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002690.3(POLB):​c.262-291T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,196 control chromosomes in the GnomAD database, including 48,052 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 0.76 (48052 hom., cov: 33)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593
• Publications: 4 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3	c.262-291T>A		intron_variant	Intron 4 of 13	ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.262-291T>A		intron_variant	Intron 4 of 13	1	NM_002690.3	ENSP00000265421.4

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115394 AN: 152078 Hom.: 48036 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.803

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.758 AC: 115432 AN: 152196 Hom.: 48052 Cov.: 33 AF XY: 0.756 AC XY: 56283 AN XY: 74404

African (AFR) AF: 0.381 AC: 15824 AN: 41486

American (AMR) AF: 0.887 AC: 13566 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3250 AN: 3472

East Asian (EAS) AF: 0.853 AC: 4420 AN: 5180

South Asian (SAS) AF: 0.778 AC: 3757 AN: 4828

European-Finnish (FIN) AF: 0.819 AC: 8672 AN: 10594

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63130 AN: 68018

Other (OTH) AF: 0.802 AC: 1694 AN: 2112

Alfa AF: 0.828 Hom.: 6876

Bravo AF: 0.750

Asia WGS AF: 0.727 AC: 2526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2976244; hg19: chr8-42207234;