ENST00000463117.6:c.-117-455C>T

Variant names:

• chr10-133526341-C-T
• rs2031920
• ENST00000463117.6:c.-117-455C>T

Variant summary

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

The ENST00000463117.6(CYP2E1):​c.-117-455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 152,114 control chromosomes in the GnomAD database, including 221 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 0.033 (221 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CYP2E1 ENST00000463117.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980
• Publications: 198 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=-0.96).
• 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: ENST00000463117.6. 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.-117-455C>T		intron	N/A	ENSP00000440689.1
	CYP2E1	ENST00000541261.1	TSL:4	c.-117-455C>T		intron	N/A	ENSP00000437799.1
	ENSG00000278518	ENST00000622716.2	TSL:6	n.1663G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5070 AN: 151996 Hom.: 215 Cov.: 33

Gnomad AFR AF: 0.00759

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0350

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: 0.0334 AC: 5082 AN: 152114 Hom.: 221 Cov.: 33 AF XY: 0.0356 AC XY: 2648 AN XY: 74368

African (AFR) AF: 0.00757 AC: 314 AN: 41502

American (AMR) AF: 0.0882 AC: 1347 AN: 15266

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

East Asian (EAS) AF: 0.204 AC: 1056 AN: 5166

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4818

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10582

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

European-Non Finnish (NFE) AF: 0.0263 AC: 1791 AN: 67998

Other (OTH) AF: 0.0351 AC: 74 AN: 2108

Alfa AF: 0.0322 Hom.: 462

Bravo AF: 0.0402

Asia WGS AF: 0.0710 AC: 249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.22
DANN	Benign	0.30
PhyloP100		-0.98
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: rs2031920; hg19: chr10-135339845;