chr10-133536297-T-C

Variant names:

• chr10-133536297-T-C
• rs1329149
• NM_000773.4:c.968-766T>C

Variant summary

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

The NM_000773.4(CYP2E1):​c.968-766T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,794 control chromosomes in the GnomAD database, including 44,700 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 0.74 (44700 hom., cov: 30)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.968-766T>C		intron_variant	Intron 6 of 8	ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.968-766T>C		intron_variant	Intron 6 of 8	1	NM_000773.4	ENSP00000252945.3

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111775 AN: 151674 Hom.: 44680 Cov.: 30

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.737 AC: 111831 AN: 151794 Hom.: 44700 Cov.: 30 AF XY: 0.741 AC XY: 54950 AN XY: 74176

African (AFR) AF: 0.380 AC: 15701 AN: 41268

American (AMR) AF: 0.802 AC: 12244 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2867 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4211 AN: 5130

South Asian (SAS) AF: 0.831 AC: 4000 AN: 4816

European-Finnish (FIN) AF: 0.923 AC: 9746 AN: 10558

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60401 AN: 67976

Other (OTH) AF: 0.754 AC: 1592 AN: 2112

Alfa AF: 0.842 Hom.: 88833

Asia WGS AF: 0.801 AC: 2787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1329149; hg19: chr10-135349801;