10-133526101-G-C

Variant names:

• chr10-133526101-G-C
• rs3813867
• ENST00000463117.6:c.-117-695G>C

Variant summary

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

The ENST00000541261.1(CYP2E1):​c.-118+460G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 152,254 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.047 (293 hom., cov: 33)
• Consequence: CYP2E1 ENST00000541261.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 172 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]

LOC105378575 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541261.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000463117.6	TSL:5	c.-117-695G>C		intron	N/A	ENSP00000440689.1
	CYP2E1	ENST00000541261.1	TSL:4	c.-118+460G>C		intron	N/A	ENSP00000437799.1
	ENSG00000278518	ENST00000822676.1		n.230+659C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7214 AN: 152136 Hom.: 286 Cov.: 33

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0475 AC: 7226 AN: 152254 Hom.: 293 Cov.: 33 AF XY: 0.0491 AC XY: 3659 AN XY: 74464

African (AFR) AF: 0.0572 AC: 2374 AN: 41516

American (AMR) AF: 0.0917 AC: 1403 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1054 AN: 5178

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4822

European-Finnish (FIN) AF: 0.0219 AC: 233 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0265 AC: 1805 AN: 68034

Other (OTH) AF: 0.0412 AC: 87 AN: 2112

Alfa AF: 0.00975 Hom.: 2

Bravo AF: 0.0565

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.70
PhyloP100		-2.7
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: rs3813867; hg19: chr10-135339605;