Genetic Variant OGG1:c.138-212C>T (chr3-9750733-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002542.6(OGG1):c.138-212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 724,558 control chromosomes in the GnomAD database, including 19 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 0.0067 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 6 hom. )

Consequence

OGG1
NM_002542.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.664

Publications

0 publications found

Variant links:

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]

OGG1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00671 (1022/152290) while in subpopulation AFR AF = 0.0223 (927/41548). AF 95% confidence interval is 0.0211. There are 13 homozygotes in GnomAd4. There are 495 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OGG1	NM_002542.6	MANE Select	c.138-212C>T	intron	N/A	NP_002533.1	O15527-1
OGG1	NM_016821.3		c.138-212C>T	intron	N/A	NP_058214.1	O15527-4
OGG1	NM_016820.4		c.138-212C>T	intron	N/A	NP_058213.1	E5KPN0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OGG1	ENST00000344629.12	TSL:1 MANE Select	c.138-212C>T	intron	N/A	ENSP00000342851.7	O15527-1
OGG1	ENST00000302036.12	TSL:1	c.138-212C>T	intron	N/A	ENSP00000306561.7	O15527-4
OGG1	ENST00000302003.11	TSL:1	c.138-212C>T	intron	N/A	ENSP00000305584.7	O15527-3

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

1022

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00621

GnomAD4 exome

AF:

0.00107

AC:

611

AN:

572268

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

282

AN XY:

300020

show subpopulations

African (AFR)

AF:

0.0225

AC:

346

AN:

15374

American (AMR)

AF:

0.00226

AC:

AN:

26548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15740

East Asian (EAS)

AF:

0.00

AC:

AN:

31740

South Asian (SAS)

AF:

0.000115

AC:

AN:

52146

European-Finnish (FIN)

AF:

0.000567

AC:

AN:

29960

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

3644

European-Non Finnish (NFE)

AF:

0.000251

AC:

AN:

366782

Other (OTH)

AF:

0.00257

AC:

AN:

30334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00671

AC:

1022

AN:

152290

Hom.:

Cov.:

AF XY:

0.00665

AC XY:

495

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0223

AC:

927

AN:

41548

American (AMR)

AF:

0.00346

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000848

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68018

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

146

194

243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00199

Hom.:

Bravo

AF:

0.00752

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.3

(source)

DANN

Benign

0.86

PhyloP100

-0.66

PromoterAI

-0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over