rs7092584

chr10-133534753-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000773.4(CYP2E1):c.967+856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,054 control chromosomes in the GnomAD database, including 1,899 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 0.14 (1899 hom., cov: 33)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4	c.967+856C>T		intron_variant		ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000252945.8	c.967+856C>T		intron_variant		1	NM_000773.4	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21581 AN: 151938 Hom.: 1898 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21591 AN: 152054 Hom.: 1899 Cov.: 33 AF XY: 0.149 AC XY: 11052 AN XY: 74304

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.137

Alfa AF: 0.113 Hom.: 1046

Bravo AF: 0.146

Asia WGS AF: 0.304 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.23
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7092584; hg19: chr10-135348257;