rs1801129

Variant names:

• chr3-9750264-A-G
• rs1801129
• NM_002542.6:c.-23A>G

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.-23A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00099 in 1,602,786 control chromosomes in the GnomAD database, including 45 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 0.00081 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (43 hom.)
• Consequence: OGG1 NM_002542.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 14 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=-0.8).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000808 (123/152240) while in subpopulation EAS AF = 0.0232 (120/5174). AF 95% confidence interval is 0.0198. There are 2 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.-23A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_002533.1	O15527-1
	OGG1	NM_002542.6	MANE Select	c.-23A>G		5_prime_UTR	Exon 1 of 7	NP_002533.1	O15527-1
	OGG1	NM_016821.3		c.-23A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_058214.1	O15527-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	ENST00000344629.12	TSL:1 MANE Select	c.-23A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000342851.7	O15527-1
	OGG1	ENST00000302036.12	TSL:1	c.-23A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000306561.7	O15527-4
	OGG1	ENST00000302003.11	TSL:1	c.-23A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000305584.7	O15527-3

Frequencies

GnomAD3 genomes AF: 0.000815 AC: 124 AN: 152122 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00120 AC: 295 AN: 244938 AF XY: 0.00105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0159

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.00101 AC: 1463 AN: 1450546 Hom.: 43 Cov.: 31 AF XY: 0.00101 AC XY: 725 AN XY: 720370

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.0000225 AC: 1 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25704

East Asian (EAS) AF: 0.0361 AC: 1429 AN: 39548

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5372

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1106112

Other (OTH) AF: 0.000450 AC: 27 AN: 59936

GnomAD4 genome AF: 0.000808 AC: 123 AN: 152240 Hom.: 2 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74444

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00107 Hom.: 9

Bravo AF: 0.000635

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.11
DANN	Benign	0.36
PhyloP100		-1.9
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs1801129; hg19: chr3-9791948; COSMIC: COSV57352891; COSMIC: COSV57352891;