rs3136790

chr8-42367498-A-C

Variant summary

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

The NM_002690.3(POLB):c.709-1773A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,078 control chromosomes in the GnomAD database, including 10,585 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 (10585 hom., cov: 32)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLB	NM_002690.3	c.709-1773A>C		intron_variant		ENST00000265421.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLB	ENST00000265421.9	c.709-1773A>C		intron_variant		1	NM_002690.3	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42664 AN: 151960 Hom.: 10545 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.281 AC: 42752 AN: 152078 Hom.: 10585 Cov.: 32 AF XY: 0.280 AC XY: 20853 AN XY: 74346

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.231

Alfa AF: 0.246 Hom.: 1902

Bravo AF: 0.290

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.073
Dann	Benign	0.50

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: rs3136790; hg19: chr8-42225016;