rs915906

Positions:

• chr10-133530234-C-T

Variant summary

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

The NM_000773.4(CYP2E1):​c.338-1351C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,072 control chromosomes in the GnomAD database, including 39,496 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 0.68 (39496 hom., cov: 33)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.338-1351C>T		intron_variant		ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.338-1351C>T		intron_variant		1	NM_000773.4	ENSP00000252945	P1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103897 AN: 151954 Hom.: 39481 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.683 AC: 103940 AN: 152072 Hom.: 39496 Cov.: 33 AF XY: 0.683 AC XY: 50800 AN XY: 74338

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.710

Alfa AF: 0.819 Hom.: 103810

Bravo AF: 0.668

Asia WGS AF: 0.690 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.62

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: rs915906; hg19: chr10-135343738;