rs2249695

Variant names:

• chr10-133538664-T-C
• rs2249695
• NM_000773.4:c.1298-116T>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.1298-116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 875,910 control chromosomes in the GnomAD database, including 243,881 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 (34643 hom., cov: 32)
  • Exomes 𝑓: 0.76 (209238 hom.)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	NM_000773.4	MANE Select	c.1298-116T>C		intron	N/A	NP_000764.1	P05181

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.1298-116T>C		intron	N/A	ENSP00000252945.3	P05181
	CYP2E1	ENST00000421586.5	TSL:1	c.1037-116T>C		intron	N/A	ENSP00000412754.1	H0Y7H4
	CYP2E1	ENST00000418356.1	TSL:1	c.887-116T>C		intron	N/A	ENSP00000397299.1	H0Y593

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97695 AN: 151674 Hom.: 34621 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.660

GnomAD4 exome AF: 0.758 AC: 549085 AN: 724118 Hom.: 209238 AF XY: 0.757 AC XY: 286697 AN XY: 378734

African (AFR) AF: 0.300 AC: 5679 AN: 18944

American (AMR) AF: 0.783 AC: 26345 AN: 33656

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 12449 AN: 16958

East Asian (EAS) AF: 0.580 AC: 20932 AN: 36118

South Asian (SAS) AF: 0.666 AC: 38991 AN: 58550

European-Finnish (FIN) AF: 0.794 AC: 36513 AN: 45980

Middle Eastern (MID) AF: 0.699 AC: 2657 AN: 3802

European-Non Finnish (NFE) AF: 0.800 AC: 379615 AN: 474498

Other (OTH) AF: 0.727 AC: 25904 AN: 35612

GnomAD4 genome AF: 0.644 AC: 97741 AN: 151792 Hom.: 34643 Cov.: 32 AF XY: 0.645 AC XY: 47820 AN XY: 74164

African (AFR) AF: 0.300 AC: 12389 AN: 41266

American (AMR) AF: 0.743 AC: 11333 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3055 AN: 5156

South Asian (SAS) AF: 0.644 AC: 3109 AN: 4826

European-Finnish (FIN) AF: 0.800 AC: 8454 AN: 10572

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54476 AN: 67942

Other (OTH) AF: 0.664 AC: 1400 AN: 2108

Alfa AF: 0.753 Hom.: 70319

Asia WGS AF: 0.630 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.47
PhyloP100		0.20
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: rs2249695; hg19: chr10-135352168;