Genetic Variant CYP2E1:c.1298-131A>G (chr10-133538649-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000773.4(CYP2E1):c.1298-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 737,398 control chromosomes in the GnomAD database, including 201,646 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 0.64 ( 34649 hom., cov: 32)

Exomes 𝑓: 0.75 ( 166997 hom. )

Consequence

CYP2E1
NM_000773.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.394

Publications

22 publications found

Variant links:

Genes affected

CYP2E1 (HGNC:2631): (cytochrome P450 family 2 subfamily E member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [provided by RefSeq, Jul 2008]

CYP2E1 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4 link	c.1298-131A>G		intron_variant	Intron 8 of 8	ENST00000252945.8	NP_000764.1	P05181

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8 link	c.1298-131A>G		intron_variant	Intron 8 of 8	1	NM_000773.4	ENSP00000252945.3		P05181

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97722

AN:

151718

Hom.:

34629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.841

Gnomad AMR

AF:

0.743

Gnomad ASJ

AF:

0.733

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.799

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.660

GnomAD4 exome

AF:

0.753

AC:

440808

AN:

585562

Hom.:

166997

AF XY:

0.751

AC XY:

232632

AN XY:

309792

show subpopulations

African (AFR)

AF:

0.301

AC:

4791

AN:

15936

American (AMR)

AF:

0.778

AC:

20680

AN:

26574

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

11032

AN:

15026

East Asian (EAS)

AF:

0.579

AC:

20250

AN:

35004

South Asian (SAS)

AF:

0.663

AC:

34409

AN:

51934

European-Finnish (FIN)

AF:

0.794

AC:

34117

AN:

42982

Middle Eastern (MID)

AF:

0.700

AC:

2238

AN:

3196

European-Non Finnish (NFE)

AF:

0.799

AC:

290993

AN:

364224

Other (OTH)

AF:

0.727

AC:

22298

AN:

30686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

4817

9635

14452

19270

24087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2732

5464

8196

10928

13660

<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:

0.644

AC:

97766

AN:

151836

Hom.:

34649

Cov.:

AF XY:

0.645

AC XY:

47843

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.300

AC:

12389

AN:

41270

American (AMR)

AF:

0.744

AC:

11351

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

2541

AN:

3466

East Asian (EAS)

AF:

0.592

AC:

3058

AN:

5164

South Asian (SAS)

AF:

0.643

AC:

3102

AN:

4824

European-Finnish (FIN)

AF:

0.799

AC:

8465

AN:

10588

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.802

AC:

54482

AN:

67944

Other (OTH)

AF:

0.663

AC:

1397

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1293

2586

3878

5171

6464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.741

Hom.:

126671

Asia WGS

AF:

0.627

AC:

2178

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.6

(source)

DANN

Benign

0.56

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over