dbSNP rs11101812: CYP2E1:c.*52T>C (chr10-133539016-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000773.4(CYP2E1):c.*52T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,465,024 control chromosomes in the GnomAD database, including 83 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 0.012 ( 45 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 38 hom. )

Consequence

CYP2E1
NM_000773.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

4 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:

Genome browser will be placed here

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=-0.91).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1890/152190) while in subpopulation AFR AF = 0.0439 (1819/41482). AF 95% confidence interval is 0.0422. There are 45 homozygotes in GnomAd4. There are 892 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4 link	c.*52T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000252945.8	NP_000764.1	P05181

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8 link	c.*52T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_000773.4	ENSP00000252945.3		P05181

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1891

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0440

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.00387

AC:

750

AN:

193902

AF XY:

0.00290

show subpopulations

Gnomad AFR exome

AF:

0.0463

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00125

AC:

1636

AN:

1312834

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

706

AN XY:

647002

show subpopulations

African (AFR)

AF:

0.0456

AC:

1331

AN:

29206

American (AMR)

AF:

0.00209

AC:

AN:

29248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21444

East Asian (EAS)

AF:

0.00

AC:

AN:

37702

South Asian (SAS)

AF:

0.0000590

AC:

AN:

67802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50510

Middle Eastern (MID)

AF:

0.00133

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

0.0000894

AC:

AN:

1017394

Other (OTH)

AF:

0.00262

AC:

142

AN:

54258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0124

AC:

1890

AN:

152190

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

892

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0439

AC:

1819

AN:

41482

American (AMR)

AF:

0.00321

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68022

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

173

259

346

432

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:

0.0109

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.2

(source)

DANN

Benign

0.46

PhyloP100

2.1

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