rs2480257

Variant names:

• chr10-133539005-T-A
• rs2480257
• NM_000773.4:c.*41T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-133539005-T-A
• chr10-133539005-T-C
• chr10-133539005-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000773.4(CYP2E1):​c.*41T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,505,476 control chromosomes in the GnomAD database, including 434,684 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 0.61 (32429 hom., cov: 31)
  • Exomes 𝑓: 0.77 (402255 hom.)
• Consequence: CYP2E1 NM_000773.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724
• Publications: 22 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	NM_000773.4	MANE Select	c.*41T>A		3_prime_UTR	Exon 9 of 9	NP_000764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.*41T>A		3_prime_UTR	Exon 9 of 9	ENSP00000252945.3
	CYP2E1	ENST00000368520.1	TSL:1	n.1358+1113T>A		intron	N/A
	CYP2E1	ENST00000469258.1	TSL:2	n.619T>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 91971 AN: 151164 Hom.: 32415 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.724

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.629

GnomAD2 exomes AF: 0.705 AC: 142053 AN: 201368 AF XY: 0.718

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.671

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.574

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.800

Gnomad OTH exome AF: 0.735

GnomAD4 exome AF: 0.767 AC: 1038435 AN: 1354196 Hom.: 402255 Cov.: 22 AF XY: 0.766 AC XY: 510602 AN XY: 666218

African (AFR) AF: 0.196 AC: 5903 AN: 30134

American (AMR) AF: 0.673 AC: 20232 AN: 30048

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 16409 AN: 22324

East Asian (EAS) AF: 0.562 AC: 21076 AN: 37518

South Asian (SAS) AF: 0.662 AC: 46199 AN: 69750

European-Finnish (FIN) AF: 0.789 AC: 40137 AN: 50894

Middle Eastern (MID) AF: 0.698 AC: 3759 AN: 5384

European-Non Finnish (NFE) AF: 0.802 AC: 844245 AN: 1052532

Other (OTH) AF: 0.728 AC: 40475 AN: 55612

GnomAD4 genome AF: 0.608 AC: 91997 AN: 151280 Hom.: 32429 Cov.: 31 AF XY: 0.608 AC XY: 44917 AN XY: 73908

African (AFR) AF: 0.209 AC: 8612 AN: 41190

American (AMR) AF: 0.667 AC: 10150 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2529 AN: 3464

East Asian (EAS) AF: 0.567 AC: 2904 AN: 5120

South Asian (SAS) AF: 0.644 AC: 3094 AN: 4808

European-Finnish (FIN) AF: 0.790 AC: 8254 AN: 10454

Middle Eastern (MID) AF: 0.724 AC: 210 AN: 290

European-Non Finnish (NFE) AF: 0.799 AC: 54151 AN: 67740

Other (OTH) AF: 0.634 AC: 1328 AN: 2096

Alfa AF: 0.698 Hom.: 6714

Asia WGS AF: 0.616 AC: 2140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2480257; hg19: chr10-135352509; COSMIC: COSV53313518; COSMIC: COSV53313518;