rs2249695

Positions:

• chr10-133538664-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.1298-116T>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

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=-0.85).
• 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	Protein	UniProt
CYP2E1	NM_000773.4	c.1298-116T>C		intron_variant		ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.1298-116T>C		intron_variant		1	NM_000773.4	ENSP00000252945.3

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

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.727

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

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.664

Alfa AF: 0.770 Hom.: 56752

Asia WGS AF: 0.630 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.47

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: rs2249695; hg19: chr10-135352168;