chr3-9753859-A-G

Variant names:

• chr3-9753859-A-G
• rs3219008
• NM_002542.6:c.566-845A>G

Variant summary

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

The NM_002542.6(OGG1):​c.566-845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,196 control chromosomes in the GnomAD database, including 6,815 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 0.28 (6815 hom., cov: 33)
• Consequence: OGG1 NM_002542.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

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.566-845A>G		intron	N/A	NP_002533.1	O15527-1
	OGG1	NM_016821.3		c.566-845A>G		intron	N/A	NP_058214.1	O15527-4
	OGG1	NM_016820.4		c.566-845A>G		intron	N/A	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.566-845A>G		intron	N/A	ENSP00000342851.7	O15527-1
	OGG1	ENST00000302036.12	TSL:1	c.566-845A>G		intron	N/A	ENSP00000306561.7	O15527-4
	OGG1	ENST00000302003.11	TSL:1	c.566-845A>G		intron	N/A	ENSP00000305584.7	O15527-3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42590 AN: 152078 Hom.: 6828 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.280 AC: 42592 AN: 152196 Hom.: 6815 Cov.: 33 AF XY: 0.276 AC XY: 20555 AN XY: 74414

African (AFR) AF: 0.399 AC: 16548 AN: 41506

American (AMR) AF: 0.275 AC: 4201 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2907 AN: 5160

South Asian (SAS) AF: 0.330 AC: 1594 AN: 4832

European-Finnish (FIN) AF: 0.146 AC: 1553 AN: 10612

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14294 AN: 68004

Other (OTH) AF: 0.267 AC: 562 AN: 2108

Alfa AF: 0.197 Hom.: 1315

Bravo AF: 0.302

Asia WGS AF: 0.386 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.54
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs3219008; hg19: chr3-9795543;