10-133540621-T-G

Variant names:

• chr10-133540621-T-G
• rs8192780
• ENST00000368520.1:n.1358+2729T>G

Variant summary

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

The ENST00000368520.1(CYP2E1):​n.1358+2729T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,914 control chromosomes in the GnomAD database, including 34,048 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 (34048 hom., cov: 33)
• Consequence: CYP2E1 ENST00000368520.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• Publications: 7 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=-1.01).
• 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: ENST00000368520.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000368520.1	TSL:1	n.1358+2729T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97750 AN: 151796 Hom.: 34036 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.644 AC: 97782 AN: 151914 Hom.: 34048 Cov.: 33 AF XY: 0.643 AC XY: 47757 AN XY: 74286

African (AFR) AF: 0.325 AC: 13433 AN: 41286

American (AMR) AF: 0.679 AC: 10380 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2538 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2942 AN: 5168

South Asian (SAS) AF: 0.646 AC: 3111 AN: 4816

European-Finnish (FIN) AF: 0.800 AC: 8482 AN: 10600

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54521 AN: 67974

Other (OTH) AF: 0.660 AC: 1395 AN: 2114

Alfa AF: 0.739 Hom.: 15488

Asia WGS AF: 0.626 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.29
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8192780; hg19: chr10-135354125;