3-9756456-C-G

Variant names:

• chr3-9756456-C-G
• rs2072668
• NM_002542.6:c.748-15C>G

Variant summary

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

The NM_016821.3(OGG1):​c.748-15C>G variant causes a 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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (5097 hom., cov: 33)
  • Exomes 𝑓: 0.25 (47112 hom.)
• Consequence: OGG1 NM_016821.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016821.3. 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
	OGG1	NM_002542.6	MANE Select	c.748-15C>G		intron	N/A	NP_002533.1
	OGG1	NM_016821.3		c.748-15C>G		intron	N/A	NP_058214.1
	OGG1	NM_016820.4		c.748-15C>G		intron	N/A	NP_058213.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	ENST00000344629.12	TSL:1 MANE Select	c.748-15C>G		intron	N/A	ENSP00000342851.7
	OGG1	ENST00000302036.12	TSL:1	c.748-15C>G		intron	N/A	ENSP00000306561.7
	OGG1	ENST00000302003.11	TSL:1	c.748-15C>G		intron	N/A	ENSP00000305584.7

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

GnomAD2 exomes AF: 0.281 AC: 70613 AN: 250874 AF XY: 0.276

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 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

African (AFR) AF: 0.265 AC: 8864 AN: 33424

American (AMR) AF: 0.346 AC: 15452 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5662 AN: 26132

East Asian (EAS) AF: 0.534 AC: 21210 AN: 39682

South Asian (SAS) AF: 0.317 AC: 27293 AN: 86224

European-Finnish (FIN) AF: 0.184 AC: 9832 AN: 53324

Middle Eastern (MID) AF: 0.321 AC: 1850 AN: 5764

European-Non Finnish (NFE) AF: 0.228 AC: 253478 AN: 1110832

Other (OTH) AF: 0.258 AC: 15597 AN: 60368

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

African (AFR) AF: 0.259 AC: 10766 AN: 41516

American (AMR) AF: 0.252 AC: 3860 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2977 AN: 5158

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4828

European-Finnish (FIN) AF: 0.193 AC: 2044 AN: 10604

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15123 AN: 67986

Other (OTH) AF: 0.243 AC: 514 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072668; hg19: chr3-9798140; COSMIC: COSV56538891; COSMIC: COSV56538891;