8-42369036-A-G

Position:

• chr8-42369036-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.709-235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 333,096 control chromosomes in the GnomAD database, including 12,544 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 0.27 (9771 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2773 hom.)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLB	NM_002690.3	c.709-235A>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.709-235A>G		intron_variant		1	NM_002690.3	ENSP00000265421.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41372 AN: 151958 Hom.: 9724 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.143 AC: 25947 AN: 181020 Hom.: 2773 Cov.: 0 AF XY: 0.141 AC XY: 13111 AN XY: 92864

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.0871

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.273 AC: 41468 AN: 152076 Hom.: 9771 Cov.: 32 AF XY: 0.272 AC XY: 20262 AN XY: 74362

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.226

Alfa AF: 0.0634 Hom.: 79

Bravo AF: 0.281

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.1
DANN	Benign	0.66

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: rs3136794; hg19: chr8-42226554;