3-9756456-C-G

Position:

• chr3-9756456-C-G

Variant summary

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

The NM_002542.6(OGG1):​c.748-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,612,638 control chromosomes in the GnomAD database, including 52,209 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 0.25 (5097 hom., cov: 33)
  • Exomes 𝑓: 0.25 (47112 hom.)
• Consequence: OGG1 NM_002542.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OGG1	NM_002542.6	c.748-15C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000344629.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGG1	ENST00000344629.12	c.748-15C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002542.6	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37864 AN: 152058 Hom.: 5106 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.246

GnomAD3 exomes AF: 0.281 AC: 70613 AN: 250874 Hom.: 11442 AF XY: 0.276 AC XY: 37470 AN XY: 135628

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.361

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.597

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.246 AC: 359238 AN: 1460462 Hom.: 47112 Cov.: 34 AF XY: 0.247 AC XY: 179362 AN XY: 726626

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.249 AC: 37853 AN: 152176 Hom.: 5097 Cov.: 33 AF XY: 0.247 AC XY: 18365 AN XY: 74394

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.243

Alfa AF: 0.227 Hom.: 747

Bravo AF: 0.260

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2072668; hg19: chr3-9798140; COSMIC: COSV56538891; COSMIC: COSV56538891;