chr8-42351446-T-C

Variant names:

• chr8-42351446-T-C
• rs3136749
• NM_002690.3:c.321-1073T>C

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.321-1073T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 152,330 control chromosomes in the GnomAD database, including 112 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 0.035 (112 hom., cov: 32)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 3 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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0353 (5375/152330) while in subpopulation NFE AF = 0.0404 (2751/68032). AF 95% confidence interval is 0.0392. There are 112 homozygotes in GnomAd4. There are 2444 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 112 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3	c.321-1073T>C		intron_variant	Intron 5 of 13	ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.321-1073T>C		intron_variant	Intron 5 of 13	1	NM_002690.3	ENSP00000265421.4

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5370 AN: 152212 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0353 AC: 5375 AN: 152330 Hom.: 112 Cov.: 32 AF XY: 0.0328 AC XY: 2444 AN XY: 74498

African (AFR) AF: 0.0404 AC: 1678 AN: 41572

American (AMR) AF: 0.0369 AC: 565 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0323 AC: 156 AN: 4826

European-Finnish (FIN) AF: 0.00678 AC: 72 AN: 10626

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0404 AC: 2751 AN: 68032

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0342 Hom.: 33

Bravo AF: 0.0366

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.67
PhyloP100		-0.0010
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: rs3136749; hg19: chr8-42208964;