10-133526369-T-C

Variant names:

• chr10-133526369-T-C
• rs2031921
• ENST00000463117.6:c.-117-427T>C

Variant summary

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

The ENST00000541261.1(CYP2E1):​c.-117-427T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,230 control chromosomes in the GnomAD database, including 275 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 0.045 (275 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CYP2E1 ENST00000541261.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 9 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]

ENSG00000278518 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 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.-117-427T>C		intron	N/A	ENSP00000440689.1
	CYP2E1	ENST00000541261.1	TSL:4	c.-117-427T>C		intron	N/A	ENSP00000437799.1
	ENSG00000278518	ENST00000622716.2	TSL:6	n.1635A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6838 AN: 152112 Hom.: 269 Cov.: 33

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0392

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0450 AC: 6848 AN: 152230 Hom.: 275 Cov.: 33 AF XY: 0.0467 AC XY: 3479 AN XY: 74438

African (AFR) AF: 0.0486 AC: 2019 AN: 41510

American (AMR) AF: 0.0909 AC: 1390 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1056 AN: 5180

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4832

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0264 AC: 1799 AN: 68020

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0124 Hom.: 3

Bravo AF: 0.0538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		2.0
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: rs2031921; hg19: chr10-135339873;