3-9750269-G-T

Variant names:

• chr3-9750269-G-T
• rs1801126
• NM_002542.6:c.-18G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002542.6(OGG1):​c.-18G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,604,704 control chromosomes in the GnomAD database, including 32 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 0.0026 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (31 hom.)
• Consequence: OGG1 NM_002542.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 15 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=-0.74).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00257 (391/152330) while in subpopulation EAS AF = 0.0189 (98/5190). AF 95% confidence interval is 0.0159. There are 1 homozygotes in GnomAd4. There are 209 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 31 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002542.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	NM_002542.6	MANE Select	c.-18G>T		5_prime_UTR	Exon 1 of 7	NP_002533.1	O15527-1
	OGG1	NM_016821.3		c.-18G>T		5_prime_UTR	Exon 1 of 7	NP_058214.1	O15527-4
	OGG1	NM_016820.4		c.-18G>T		5_prime_UTR	Exon 1 of 7	NP_058213.1	E5KPN0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	ENST00000344629.12	TSL:1 MANE Select	c.-18G>T		5_prime_UTR	Exon 1 of 7	ENSP00000342851.7	O15527-1
	OGG1	ENST00000302036.12	TSL:1	c.-18G>T		5_prime_UTR	Exon 1 of 7	ENSP00000306561.7	O15527-4
	OGG1	ENST00000302003.11	TSL:1	c.-18G>T		5_prime_UTR	Exon 1 of 7	ENSP00000305584.7	O15527-3

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 152212 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0188

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00442 AC: 1088 AN: 246080 AF XY: 0.00364

Gnomad AFR exome AF: 0.000434

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.00761

Gnomad EAS exome AF: 0.0171

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.00169 AC: 2456 AN: 1452374 Hom.: 31 Cov.: 31 AF XY: 0.00157 AC XY: 1135 AN XY: 721416

African (AFR) AF: 0.000270 AC: 9 AN: 33364

American (AMR) AF: 0.0191 AC: 848 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00647 AC: 167 AN: 25814

East Asian (EAS) AF: 0.0280 AC: 1109 AN: 39556

South Asian (SAS) AF: 0.000501 AC: 43 AN: 85848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50820

Middle Eastern (MID) AF: 0.000368 AC: 2 AN: 5438

European-Non Finnish (NFE) AF: 0.000163 AC: 180 AN: 1107030

Other (OTH) AF: 0.00163 AC: 98 AN: 60010

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152330 Hom.: 1 Cov.: 33 AF XY: 0.00281 AC XY: 209 AN XY: 74494

African (AFR) AF: 0.000553 AC: 23 AN: 41580

American (AMR) AF: 0.0154 AC: 236 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68006

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00146 Hom.: 7

Bravo AF: 0.00416

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.0
DANN	Benign	0.86
PhyloP100		1.0
PromoterAI		0.094	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	polymorphism

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: rs1801126; hg19: chr3-9791953;