rs2864987

Positions:

• chr10-133535075-A-G

Variant summary

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

The NM_000773.4(CYP2E1):​c.967+1178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 151,850 control chromosomes in the GnomAD database, including 925 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 0.10 (925 hom., cov: 31)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-1.09).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4	c.967+1178A>G		intron_variant		ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000252945.8	c.967+1178A>G		intron_variant		1	NM_000773.4	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15425 AN: 151730 Hom.: 921 Cov.: 31

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.0883

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.102 AC: 15448 AN: 151850 Hom.: 925 Cov.: 31 AF XY: 0.106 AC XY: 7904 AN XY: 74230

Gnomad4 AFR AF: 0.0807

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0943

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0892

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.0937 Hom.: 81

Bravo AF: 0.101

Asia WGS AF: 0.181 AC: 631 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.38
DANN	Benign	0.18

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: rs2864987; hg19: chr10-135348579;