8-42342820-T-C

Variant names:

• chr8-42342820-T-C
• rs2953993
• NM_002690.3:c.120-2133T>C

Variant summary

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

The NM_002690.3(POLB):​c.120-2133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 151,844 control chromosomes in the GnomAD database, including 48,260 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 0.76 (48260 hom., cov: 29)
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• 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]

RPL5P23 (HGNC:36553): (ribosomal protein L5 pseudogene 23)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLB	NM_002690.3	MANE Select	c.120-2133T>C		intron	N/A	NP_002681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLB	ENST00000265421.9	TSL:1 MANE Select	c.120-2133T>C		intron	N/A	ENSP00000265421.4
	POLB	ENST00000518925.5	TSL:5	c.120-2133T>C		intron	N/A	ENSP00000430784.1
	POLB	ENST00000520008.5	TSL:2	c.-343-2133T>C		intron	N/A	ENSP00000430610.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115846 AN: 151726 Hom.: 48242 Cov.: 29

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.763 AC: 115891 AN: 151844 Hom.: 48260 Cov.: 29 AF XY: 0.761 AC XY: 56499 AN XY: 74234

African (AFR) AF: 0.396 AC: 16348 AN: 41274

American (AMR) AF: 0.888 AC: 13569 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3250 AN: 3468

East Asian (EAS) AF: 0.853 AC: 4396 AN: 5152

South Asian (SAS) AF: 0.780 AC: 3739 AN: 4796

European-Finnish (FIN) AF: 0.819 AC: 8653 AN: 10564

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63118 AN: 67998

Other (OTH) AF: 0.804 AC: 1698 AN: 2112

Alfa AF: 0.843 Hom.: 13179

Bravo AF: 0.755

Asia WGS AF: 0.729 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.92
DANN	Benign	0.26
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2953993; hg19: chr8-42200338;