chr8-42367665-T-G

Variant names:

• chr8-42367665-T-G
• rs3136791
• NM_002690.3:c.709-1606T>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.709-1606T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,266 control chromosomes in the GnomAD database, including 131 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 0.038 (131 hom., cov: 32)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• 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=-0.85).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0385 (5855/152266) while in subpopulation AFR AF = 0.0514 (2135/41524). AF 95% confidence interval is 0.0496. There are 131 homozygotes in GnomAd4. There are 2675 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 131 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002690.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLB	NM_002690.3	MANE Select	c.709-1606T>G		intron	N/A	NP_002681.1	P06746

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLB	ENST00000265421.9	TSL:1 MANE Select	c.709-1606T>G		intron	N/A	ENSP00000265421.4	P06746
	POLB	ENST00000929417.1		c.709-1606T>G		intron	N/A	ENSP00000599476.1
	POLB	ENST00000518925.5	TSL:5	c.814-1606T>G		intron	N/A	ENSP00000430784.1	E7EW18

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5851 AN: 152148 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.00687

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0385 AC: 5855 AN: 152266 Hom.: 131 Cov.: 32 AF XY: 0.0359 AC XY: 2675 AN XY: 74480

African (AFR) AF: 0.0514 AC: 2135 AN: 41524

American (AMR) AF: 0.0382 AC: 585 AN: 15296

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4824

European-Finnish (FIN) AF: 0.00687 AC: 73 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0404 AC: 2746 AN: 68016

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0379 Hom.: 28

Bravo AF: 0.0402

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		0.043
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: rs3136791; hg19: chr8-42225183;