rs2480258

Positions:

• chr10-133538596-T-C

Variant summary

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

The NM_000773.4(CYP2E1):​c.1298-184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,810 control chromosomes in the GnomAD database, including 33,790 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 0.64 (33790 hom., cov: 32)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.866

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4	c.1298-184T>C		intron_variant		ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000252945.8	c.1298-184T>C		intron_variant		1	NM_000773.4	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96459 AN: 151692 Hom.: 33776 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.636 AC: 96492 AN: 151810 Hom.: 33790 Cov.: 32 AF XY: 0.635 AC XY: 47122 AN XY: 74196

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.652

Alfa AF: 0.766 Hom.: 57105

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2480258; hg19: chr10-135352100;