rs915907

chr10-133533423-C-A

Variant summary

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

The NM_000773.4(CYP2E1):c.826-333C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,134 control chromosomes in the GnomAD database, including 2,652 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 0.18 (2652 hom., cov: 33)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4	c.826-333C>A		intron_variant		ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000252945.8	c.826-333C>A		intron_variant		1	NM_000773.4	P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26943 AN: 152016 Hom.: 2654 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.177 AC: 26951 AN: 152134 Hom.: 2652 Cov.: 33 AF XY: 0.184 AC XY: 13677 AN XY: 74364

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.160

Alfa AF: 0.161 Hom.: 2705

Bravo AF: 0.174

Asia WGS AF: 0.316 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	2.3
Dann	Benign	0.91

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: rs915907; hg19: chr10-135346927;