chr8-42342689-G-C

Variant names:

• chr8-42342689-G-C
• rs2979895
• NM_002690.3:c.120-2264G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002690.3(POLB):​c.120-2264G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLB NM_002690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

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.120-2264G>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.120-2264G>C		intron	N/A	ENSP00000265421.4
	POLB	ENST00000518925.5	TSL:5	c.120-2264G>C		intron	N/A	ENSP00000430784.1
	POLB	ENST00000520008.5	TSL:2	c.-343-2264G>C		intron	N/A	ENSP00000430610.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 341548 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 183074

African (AFR) AF: 0.00 AC: 0 AN: 9814

American (AMR) AF: 0.00 AC: 0 AN: 14454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10214

East Asian (EAS) AF: 0.00 AC: 0 AN: 20764

South Asian (SAS) AF: 0.00 AC: 0 AN: 41004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 206034

Other (OTH) AF: 0.00 AC: 0 AN: 19246

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.26
DANN	Benign	0.21
PhyloP100		-1.6

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: rs2979895; hg19: chr8-42200207;