rs55897648

chr10-133537760-G-Achr10-133537760-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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]

ACMG classification

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 GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4	c.1165G>A	p.Val389Ile	missense_variant	8/9	ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000252945.8	c.1165G>A	p.Val389Ile	missense_variant	8/9	1	NM_000773.4	P1

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 304 AN: 152122 Hom.: 1 Cov.: 33

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.: 2 AF XY: 0.00203 AC XY: 276 AN XY: 135642

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.: 10 Cov.: 31 AF XY: 0.00259 AC XY: 1883 AN XY: 726858

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.: 1 Cov.: 33 AF XY: 0.00246 AC XY: 183 AN XY: 74442

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.: 1

Bravo AF: 0.00141

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00163 AC: 14

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	T
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	N
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.0036	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.95	L;L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
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	T
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

Other links and lift over

dbSNP: rs55897648; hg19: chr10-135351264; COSMIC: COSV53315775; COSMIC: COSV53315775;