3-9754442-A-G

Position:

• chr3-9754442-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002542.6(OGG1):​c.566-262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,184 control chromosomes in the GnomAD database, including 1,703 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 0.13 (1703 hom., cov: 33)
• Consequence: OGG1 NM_002542.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

Genes affected

OGG1 (HGNC:8125): (8-oxoguanine DNA glycosylase) This gene encodes the enzyme responsible for the excision of 8-oxoguanine, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen. The action of this enzyme includes lyase activity for chain cleavage. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants share the N-terminal region in common, which contains a mitochondrial targeting signal that is essential for mitochondrial localization. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OGG1	NM_002542.6	c.566-262A>G		intron_variant		ENST00000344629.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGG1	ENST00000344629.12	c.566-262A>G		intron_variant		1	NM_002542.6	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20481 AN: 152066 Hom.: 1703 Cov.: 33

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.135 AC: 20492 AN: 152184 Hom.: 1703 Cov.: 33 AF XY: 0.136 AC XY: 10095 AN XY: 74382

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0975

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.123

Alfa AF: 0.148 Hom.: 1787

Bravo AF: 0.121

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs159150; hg19: chr3-9796126;