Variant rs55897648 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000773.4(CYP2E1):c.1165G>A(p.Val389Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,613,374 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 10 hom. )

Consequence

CYP2E1
NM_000773.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

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:

CYP2E1 (HGNC:):

CYP2E1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035592318).

BP6

Variant 10-133537760-G-A is Benign according to our data. Variant chr10-133537760-G-A is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2E1	NM_000773.4 linkuse as main transcript	c.1165G>A	p.Val389Ile	missense_variant	8/9	ENST00000252945.8	NP_000764.1	P05181

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8 linkuse as main transcript	c.1165G>A	p.Val389Ile	missense_variant	8/9	1	NM_000773.4	ENSP00000252945.3		P05181

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

304

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00209

AC:

525

AN:

250976

Hom.:

AF XY:

0.00203

AC XY:

276

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000623

Gnomad FIN exome

AF:

0.00851

Gnomad NFE exome

AF:

0.00231

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00266

AC:

3890

AN:

1461134

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1883

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000627

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000650

Gnomad4 FIN exome

AF:

0.00832

Gnomad4 NFE exome

AF:

0.00284

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.00200

AC:

304

AN:

152240

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00141

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00172

AC:

209

EpiCase

AF:

0.00186

EpiControl

AF:

0.00219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.013

DANN

Benign

0.30

DEOGEN2

Benign

0.050

T;T;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.58

.;T;T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.0036

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.95

L;L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

0.17

N;N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.64

T;T;T;T

Sift4G

Benign

0.59

T;T;T;T

Polyphen

0.0030

B;B;.;.

Vest4

0.087

MVP

0.26

MPC

0.25

ClinPred

0.00047

GERP RS

-8.6

Varity_R

0.042

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over