rs3136744

Variant names:

• chr8-42349829-A-C
• rs3136744
• NM_002690.3:c.262-178A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002690.3(POLB):​c.262-178A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,210 control chromosomes in the GnomAD database, including 1,233 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 0.092 (1233 hom., cov: 32)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3	c.262-178A>C		intron_variant	Intron 4 of 13	ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.262-178A>C		intron_variant	Intron 4 of 13	1	NM_002690.3	ENSP00000265421.4

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14031 AN: 152092 Hom.: 1232 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0898

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

GnomAD4 genome AF: 0.0924 AC: 14060 AN: 152210 Hom.: 1233 Cov.: 32 AF XY: 0.0954 AC XY: 7099 AN XY: 74432

African (AFR) AF: 0.228 AC: 9472 AN: 41510

American (AMR) AF: 0.0435 AC: 666 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3472

East Asian (EAS) AF: 0.0966 AC: 500 AN: 5178

South Asian (SAS) AF: 0.0481 AC: 232 AN: 4822

European-Finnish (FIN) AF: 0.106 AC: 1122 AN: 10598

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0261 AC: 1777 AN: 68026

Other (OTH) AF: 0.0922 AC: 194 AN: 2104

Alfa AF: 0.0559 Hom.: 905

Bravo AF: 0.0942

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.6
DANN	Benign	0.75
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3136744; hg19: chr8-42207347; COSMIC: COSV55349537; COSMIC: COSV55349537;