rs2480258

Variant names:

• chr10-133538596-T-C
• rs2480258
• NM_000773.4:c.1298-184T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.1298-184T>C		intron_variant	Intron 8 of 8	ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.1298-184T>C		intron_variant	Intron 8 of 8	1	NM_000773.4	ENSP00000252945.3

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

African (AFR) AF: 0.297 AC: 12270 AN: 41250

American (AMR) AF: 0.678 AC: 10346 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2546 AN: 3472

East Asian (EAS) AF: 0.570 AC: 2940 AN: 5160

South Asian (SAS) AF: 0.644 AC: 3103 AN: 4816

European-Finnish (FIN) AF: 0.799 AC: 8449 AN: 10568

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54483 AN: 67960

Other (OTH) AF: 0.652 AC: 1375 AN: 2108

Alfa AF: 0.760 Hom.: 67568

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
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2480258; hg19: chr10-135352100;