rs3136739

Variant names:

• chr8-42347562-A-G
• rs3136739
• NM_002690.3:c.187-1454A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002690.3(POLB):​c.187-1454A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 152,082 control chromosomes in the GnomAD database, including 77 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 0.028 (77 hom., cov: 31)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 15 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0282 (4286/152082) while in subpopulation NFE AF = 0.0394 (2674/67946). AF 95% confidence interval is 0.0381. There are 77 homozygotes in GnomAd4. There are 1920 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 77 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3	c.187-1454A>G		intron_variant	Intron 3 of 13	ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.187-1454A>G		intron_variant	Intron 3 of 13	1	NM_002690.3	ENSP00000265421.4

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4280 AN: 151962 Hom.: 77 Cov.: 31

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0282 AC: 4286 AN: 152082 Hom.: 77 Cov.: 31 AF XY: 0.0258 AC XY: 1920 AN XY: 74336

African (AFR) AF: 0.0197 AC: 817 AN: 41504

American (AMR) AF: 0.0348 AC: 531 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4826

European-Finnish (FIN) AF: 0.00681 AC: 72 AN: 10578

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0394 AC: 2674 AN: 67946

Other (OTH) AF: 0.0260 AC: 55 AN: 2114

Alfa AF: 0.0305 Hom.: 32

Bravo AF: 0.0300

Asia WGS AF: 0.00925 AC: 32 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.87
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

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: rs3136739; hg19: chr8-42205080;