rs3136749

Positions:

• chr8-42351446-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 112 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLB	NM_002690.3	c.321-1073T>C		intron_variant		ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.321-1073T>C		intron_variant		1	NM_002690.3	ENSP00000265421	P1

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

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0323

Gnomad4 FIN AF: 0.00678

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0343 Hom.: 16

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

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: rs3136749; hg19: chr8-42208964;