chr10-133543735-A-C

Position:

• chr10-133543735-A-C

Variant summary

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

The ENST00000368520.1(CYP2E1):​n.1358+5843A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,970 control chromosomes in the GnomAD database, including 34,627 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 0.63 (34627 hom., cov: 33)
• Consequence: CYP2E1 ENST00000368520.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000368520.1	n.1358+5843A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95055 AN: 151854 Hom.: 34614 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.626 AC: 95082 AN: 151970 Hom.: 34627 Cov.: 33 AF XY: 0.625 AC XY: 46465 AN XY: 74288

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.653

Alfa AF: 0.779 Hom.: 61538

Bravo AF: 0.598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1536826; hg19: chr10-135357239;