rs743535

Positions:

• chr10-133535863-G-A

Variant summary

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

The NM_000773.4(CYP2E1):​c.968-1200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,182 control chromosomes in the GnomAD database, including 1,427 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 0.13 (1427 hom., cov: 33)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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]

CYP2E1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.968-1200G>A		intron_variant		ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.968-1200G>A		intron_variant		1	NM_000773.4	ENSP00000252945.3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19381 AN: 152064 Hom.: 1421 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.128 AC: 19411 AN: 152182 Hom.: 1427 Cov.: 33 AF XY: 0.132 AC XY: 9784 AN XY: 74400

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0893

Gnomad4 OTH AF: 0.114

Alfa AF: 0.100 Hom.: 1057

Bravo AF: 0.131

Asia WGS AF: 0.186 AC: 649 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	0.26
DANN	Benign	0.26

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: rs743535; hg19: chr10-135349367;