rs3813870

Positions:

• chr10-133526466-A-G

Variant summary

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

The ENST00000541261.1(CYP2E1):​c.-117-330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,202 control chromosomes in the GnomAD database, including 624 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 0.068 (624 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2E1 ENST00000541261.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105378575	XR_007062396.1	n.494T>C		non_coding_transcript_exon_variant	1/5
LOC105378575	XR_946512.3	n.200+294T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-117-330A>G		intron_variant		5		ENSP00000440689.1
CYP2E1	ENST00000541261.1	c.-117-330A>G		intron_variant		4		ENSP00000437799.1
ENSG00000278518	ENST00000622716.1	n.1048T>C		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10309 AN: 152084 Hom.: 624 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0675

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0678 AC: 10312 AN: 152202 Hom.: 624 Cov.: 33 AF XY: 0.0713 AC XY: 5303 AN XY: 74416

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0769

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0418 Hom.: 22

Bravo AF: 0.0706

Asia WGS AF: 0.231 AC: 802 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.47

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: rs3813870; hg19: chr10-135339970;