8-42338429-G-T

Variant names:

• chr8-42338429-G-T
• rs2307158
• NM_002690.3:c.-196G>T

Variant summary

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

The NM_002690.3(POLB):​c.-196G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 399,750 control chromosomes in the GnomAD database, including 5,597 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 0.15 (3598 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1999 hom.)
• Consequence: POLB NM_002690.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 7 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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3	c.-196G>T		upstream_gene_variant		ENST00000265421.9	NP_002681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLB	ENST00000265421.9	c.-196G>T		upstream_gene_variant		1	NM_002690.3	ENSP00000265421.4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 22932 AN: 148156 Hom.: 3585 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.0322

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.103 AC: 25958 AN: 251458 Hom.: 1999 Cov.: 3 AF XY: 0.109 AC XY: 15058 AN XY: 138156

African (AFR) AF: 0.432 AC: 3611 AN: 8362

American (AMR) AF: 0.0606 AC: 811 AN: 13374

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 196 AN: 5536

East Asian (EAS) AF: 0.198 AC: 2831 AN: 14322

South Asian (SAS) AF: 0.194 AC: 8706 AN: 44890

European-Finnish (FIN) AF: 0.126 AC: 1921 AN: 15288

Middle Eastern (MID) AF: 0.0917 AC: 80 AN: 872

European-Non Finnish (NFE) AF: 0.0474 AC: 6448 AN: 136108

Other (OTH) AF: 0.107 AC: 1354 AN: 12706

GnomAD4 genome AF: 0.155 AC: 22984 AN: 148292 Hom.: 3598 Cov.: 32 AF XY: 0.160 AC XY: 11581 AN XY: 72412

African (AFR) AF: 0.403 AC: 16478 AN: 40888

American (AMR) AF: 0.0686 AC: 1019 AN: 14862

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 70 AN: 3434

East Asian (EAS) AF: 0.150 AC: 708 AN: 4734

South Asian (SAS) AF: 0.210 AC: 942 AN: 4480

European-Finnish (FIN) AF: 0.125 AC: 1214 AN: 9744

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0333 AC: 2227 AN: 66910

Other (OTH) AF: 0.136 AC: 283 AN: 2078

Alfa AF: 0.0471 Hom.: 188

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.93
PhyloP100		-0.42
PromoterAI		0.018	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2307158; hg19: chr8-42195947;