Genetic Variant CYP2E1:c.1156-118G>C (chr10-133537633-G-C) – 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.1156-118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 902,148 control chromosomes in the GnomAD database, including 324,270 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 0.74 ( 44458 hom., cov: 33)

Exomes 𝑓: 0.86 ( 279812 hom. )

Consequence

CYP2E1
NM_000773.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Publications

58 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4 link	c.1156-118G>C		intron_variant	Intron 7 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.1156-118G>C		intron_variant	Intron 7 of 8	1	NM_000773.4	ENSP00000252945.3		P05181

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111630

AN:

151794

Hom.:

44438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.928

Gnomad AMR

AF:

0.800

Gnomad ASJ

AF:

0.826

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.923

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.888

Gnomad OTH

AF:

0.747

GnomAD4 exome

AF:

0.862

AC:

646615

AN:

750236

Hom.:

279812

Cov.:

AF XY:

0.862

AC XY:

331611

AN XY:

384482

show subpopulations

African (AFR)

AF:

0.366

AC:

7014

AN:

19160

American (AMR)

AF:

0.819

AC:

18509

AN:

22592

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

12960

AN:

15704

East Asian (EAS)

AF:

0.831

AC:

28935

AN:

34804

South Asian (SAS)

AF:

0.845

AC:

43485

AN:

51474

European-Finnish (FIN)

AF:

0.914

AC:

36293

AN:

39696

Middle Eastern (MID)

AF:

0.764

AC:

2882

AN:

3774

European-Non Finnish (NFE)

AF:

0.885

AC:

466689

AN:

527110

Other (OTH)

AF:

0.831

AC:

29848

AN:

35922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

3711

7422

11132

14843

18554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7404

14808

22212

29616

37020

<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:

0.735

AC:

111685

AN:

151912

Hom.:

44458

Cov.:

AF XY:

0.739

AC XY:

54905

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.375

AC:

15481

AN:

41230

American (AMR)

AF:

0.800

AC:

12227

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.826

AC:

2866

AN:

3468

East Asian (EAS)

AF:

0.821

AC:

4253

AN:

5182

South Asian (SAS)

AF:

0.830

AC:

3995

AN:

4814

European-Finnish (FIN)

AF:

0.923

AC:

9792

AN:

10608

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.888

AC:

60419

AN:

68012

Other (OTH)

AF:

0.750

AC:

1583

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1015

2030

3046

4061

5076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.713

Hom.:

2147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.65

PhyloP100

-0.021

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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