10-133527063-A-T

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378575	XR_007062396.1	n.-104T>A		upstream_gene_variant
LOC105378575	XR_946512.3	n.-104T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-40+190A>T		intron_variant	Intron 2 of 10	5		ENSP00000440689.1
CYP2E1	ENST00000541261.1	c.-40+190A>T		intron_variant	Intron 2 of 3	4		ENSP00000437799.1
ENSG00000278518	ENST00000622716.1	n.451T>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

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

Gnomad4 AFR exome AF: 0.314 AC: 2047 AN: 6526

Gnomad4 AMR exome AF: 0.685 AC: 3850 AN: 5622

Gnomad4 ASJ exome AF: 0.742 AC: 3421 AN: 4608

Gnomad4 EAS exome AF: 0.546 AC: 5368 AN: 9834

Gnomad4 SAS exome AF: 0.637 AC: 3420 AN: 5372

Gnomad4 FIN exome AF: 0.865 AC: 6144 AN: 7104

Gnomad4 NFE exome AF: 0.826 AC: 85511 AN: 103482

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.318 AC: 0.317914 AN: 0.317914

Gnomad4 AMR AF: 0.703 AC: 0.703209 AN: 0.703209

Gnomad4 ASJ AF: 0.749 AC: 0.748991 AN: 0.748991

Gnomad4 EAS AF: 0.577 AC: 0.576759 AN: 0.576759

Gnomad4 SAS AF: 0.648 AC: 0.648133 AN: 0.648133

Gnomad4 FIN AF: 0.898 AC: 0.898303 AN: 0.898303

Gnomad4 NFE AF: 0.849 AC: 0.849298 AN: 0.849298

Gnomad4 OTH AF: 0.695 AC: 0.694602 AN: 0.694602

Alfa AF: 0.737 Hom.: 4831

Asia WGS AF: 0.626 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.77
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

Publications

LitVar

Other links and lift over

dbSNP: rs2070673; hg19: chr10-135340567;