Genetic Variant ENSG00000278518:n.679C>A (chr10-133527325-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000622716.2(ENSG00000278518):n.679C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,457,132 control chromosomes in the GnomAD database, including 2,163 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 0.039 ( 150 hom., cov: 34)

Exomes 𝑓: 0.051 ( 2013 hom. )

Consequence

ENSG00000278518
ENST00000622716.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.456

Publications

37 publications found

Variant links:

Genes affected

ENSG00000278518 (HGNC:):

ENSG00000278518 links:

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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4 link	c.-71G>T		upstream_gene_variant		ENST00000252945.8	NP_000764.1	P05181

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8 link	c.-71G>T		upstream_gene_variant		1	NM_000773.4	ENSP00000252945.3		P05181

Frequencies

GnomAD3 genomes

AF:

0.0394

AC:

5907

AN:

149802

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.0353

Gnomad AMR

AF:

0.0354

Gnomad ASJ

AF:

0.0770

Gnomad EAS

AF:

0.00342

Gnomad SAS

AF:

0.0728

Gnomad FIN

AF:

0.0262

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.0494

GnomAD4 exome

AF:

0.0511

AC:

66804

AN:

1307210

Hom.:

2013

Cov.:

AF XY:

0.0516

AC XY:

33246

AN XY:

644540

show subpopulations

African (AFR)

AF:

0.0155

AC:

463

AN:

29900

American (AMR)

AF:

0.0264

AC:

892

AN:

33762

Ashkenazi Jewish (ASJ)

AF:

0.0752

AC:

1549

AN:

20594

East Asian (EAS)

AF:

0.000702

AC:

AN:

38438

South Asian (SAS)

AF:

0.0664

AC:

4779

AN:

71944

European-Finnish (FIN)

AF:

0.0304

AC:

1205

AN:

39652

Middle Eastern (MID)

AF:

0.0798

AC:

291

AN:

3648

European-Non Finnish (NFE)

AF:

0.0540

AC:

54752

AN:

1014824

Other (OTH)

AF:

0.0523

AC:

2846

AN:

54448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2953

5907

8860

11814

14767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2060

4120

6180

8240

10300

<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:

0.0395

AC:

5915

AN:

149922

Hom.:

150

Cov.:

AF XY:

0.0394

AC XY:

2882

AN XY:

73070

show subpopulations

African (AFR)

AF:

0.0174

AC:

707

AN:

40672

American (AMR)

AF:

0.0354

AC:

529

AN:

14962

Ashkenazi Jewish (ASJ)

AF:

0.0770

AC:

266

AN:

3456

East Asian (EAS)

AF:

0.00343

AC:

AN:

4962

South Asian (SAS)

AF:

0.0733

AC:

339

AN:

4624

European-Finnish (FIN)

AF:

0.0262

AC:

272

AN:

10384

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0537

AC:

3628

AN:

67594

Other (OTH)

AF:

0.0488

AC:

101

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

294

589

883

1178

1472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0508

Hom.:

555

Bravo

AF:

0.0373

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.54

PhyloP100

-0.46

PromoterAI

-0.053

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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