rs2070673

Variant names:

• chr10-133527063-A-T
• rs2070673
• ENST00000463117.6:c.-40+190A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000541261.1(CYP2E1):​c.-40+190A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 304,230 control chromosomes in the GnomAD database, including 83,504 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 0.67 (38112 hom., cov: 33)
  • Exomes 𝑓: 0.77 (45392 hom.)
• Consequence: CYP2E1 ENST00000541261.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 68 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]

ENSG00000278518 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541261.1. 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	ENST00000463117.6	TSL:5	c.-40+190A>T		intron	N/A	ENSP00000440689.1	P05181
	CYP2E1	ENST00000541261.1	TSL:4	c.-40+190A>T		intron	N/A	ENSP00000437799.1	F5H694
	ENSG00000278518	ENST00000622716.2	TSL:6	n.941T>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102273 AN: 151858 Hom.: 38095 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.768 AC: 116879 AN: 152254 Hom.: 45392 Cov.: 4 AF XY: 0.769 AC XY: 58802 AN XY: 76452

African (AFR) AF: 0.314 AC: 2047 AN: 6526

American (AMR) AF: 0.685 AC: 3850 AN: 5622

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 3421 AN: 4608

East Asian (EAS) AF: 0.546 AC: 5368 AN: 9834

South Asian (SAS) AF: 0.637 AC: 3420 AN: 5372

European-Finnish (FIN) AF: 0.865 AC: 6144 AN: 7104

Middle Eastern (MID) AF: 0.704 AC: 483 AN: 686

European-Non Finnish (NFE) AF: 0.826 AC: 85511 AN: 103482

Other (OTH) AF: 0.736 AC: 6635 AN: 9020

GnomAD4 genome AF: 0.673 AC: 102311 AN: 151976 Hom.: 38112 Cov.: 33 AF XY: 0.674 AC XY: 50066 AN XY: 74302

African (AFR) AF: 0.318 AC: 13147 AN: 41354

American (AMR) AF: 0.703 AC: 10738 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2983 AN: 5172

South Asian (SAS) AF: 0.648 AC: 3124 AN: 4820

European-Finnish (FIN) AF: 0.898 AC: 9531 AN: 10610

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57720 AN: 67962

Other (OTH) AF: 0.695 AC: 1467 AN: 2112

Alfa AF: 0.737 Hom.: 4831

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	-0.85
CADD	Benign	2.0
DANN	Benign	0.77
PhyloP100		-0.14
PromoterAI		0.00020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -2

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

Other links and lift over

dbSNP: rs2070673; hg19: chr10-135340567;