rs2979895

Positions:

• chr8-42342689-G-A
• chr8-42342689-G-C
• chr8-42342689-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002690.3(POLB):​c.120-2264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 493,080 control chromosomes in the GnomAD database, including 183,520 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 (48251 hom., cov: 30)
  • Exomes 𝑓: 0.88 (135269 hom.)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• 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/exons	MANE	Protein	UniProt
POLB	NM_002690.3	c.120-2264G>A		intron_variant		ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.120-2264G>A		intron_variant		1	NM_002690.3	ENSP00000265421	P1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115854 AN: 151826 Hom.: 48233 Cov.: 30

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.884 AC: 301725 AN: 341136 Hom.: 135269 AF XY: 0.881 AC XY: 161153 AN XY: 182820

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.914

Gnomad4 ASJ exome AF: 0.932

Gnomad4 EAS exome AF: 0.850

Gnomad4 SAS exome AF: 0.796

Gnomad4 FIN exome AF: 0.847

Gnomad4 NFE exome AF: 0.929

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.763 AC: 115899 AN: 151944 Hom.: 48251 Cov.: 30 AF XY: 0.761 AC XY: 56490 AN XY: 74248

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.804

Alfa AF: 0.831 Hom.: 6896

Bravo AF: 0.755

Asia WGS AF: 0.729 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.23

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

LitVar

Other links and lift over

dbSNP: rs2979895; hg19: chr8-42200207;