rs2272615

Positions:

• chr8-42361530-A-G

Variant summary

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

The NM_002690.3(POLB):​c.621+165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 611,534 control chromosomes in the GnomAD database, including 17,858 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 0.28 (10253 hom., cov: 33)
  • Exomes 𝑓: 0.15 (7605 hom.)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLB	NM_002690.3	c.621+165A>G		intron_variant		ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.621+165A>G		intron_variant		1	NM_002690.3	ENSP00000265421	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42168 AN: 152086 Hom.: 10207 Cov.: 33

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.150 AC: 68673 AN: 459330 Hom.: 7605 Cov.: 4 AF XY: 0.151 AC XY: 36787 AN XY: 244250

Gnomad4 AFR exome AF: 0.664

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0874

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.278 AC: 42262 AN: 152204 Hom.: 10253 Cov.: 33 AF XY: 0.277 AC XY: 20623 AN XY: 74404

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.228

Alfa AF: 0.174 Hom.: 916

Bravo AF: 0.287

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.55

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: rs2272615; hg19: chr8-42219048;