8-42338429-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_002690.3(POLB):​c.-196G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. 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 0.000034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLB NM_002690.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0107 (2669/248906) while in subpopulation MID AF= 0.0234 (20/856). AF 95% confidence interval is 0.0155. There are 0 homozygotes in gnomad4_exome. There are 1349 alleles in male gnomad4_exome subpopulation. Median coverage is 3. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLB	NM_002690.3	c.-196G>C		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>C		upstream_gene_variant		1	NM_002690.3	ENSP00000265421.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5 AN: 148202 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000422

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0107 AC: 2669 AN: 248906 Hom.: 0 Cov.: 3 AF XY: 0.00986 AC XY: 1349 AN XY: 136814

Gnomad4 AFR exome AF: 0.00523

Gnomad4 AMR exome AF: 0.00646

Gnomad4 ASJ exome AF: 0.0245

Gnomad4 EAS exome AF: 0.0136

Gnomad4 SAS exome AF: 0.000334

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.0124

Gnomad4 OTH exome AF: 0.0166

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000337 AC: 5 AN: 148338 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72432

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000422

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000103

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2307158; hg19: chr8-42195947;