10-133526589-T-C

Position:

• chr10-133526589-T-C

Variant summary

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

The ENST00000541261.1(CYP2E1):​c.-117-207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,656 control chromosomes in the GnomAD database, including 1,882 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 0.13 (1880 hom., cov: 33)
  • Exomes 𝑓: 0.17 (2 hom.)
• Consequence: CYP2E1 ENST00000541261.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105378575	XR_007062396.1	n.371A>G		non_coding_transcript_exon_variant	1/5
LOC105378575	XR_946512.3	n.200+171A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-117-207T>C		intron_variant		5		ENSP00000440689.1
CYP2E1	ENST00000541261.1	c.-117-207T>C		intron_variant		4		ENSP00000437799.1
ENSG00000278518	ENST00000622716.1	n.925A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19115 AN: 151894 Hom.: 1866 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0485

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.174 AC: 112 AN: 644 Hom.: 2 Cov.: 2 AF XY: 0.169 AC XY: 53 AN XY: 314

Gnomad4 AFR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.126 AC: 19164 AN: 152012 Hom.: 1880 Cov.: 33 AF XY: 0.125 AC XY: 9287 AN XY: 74354

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0842

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.106

Alfa AF: 0.119 Hom.: 199

Asia WGS AF: 0.0880 AC: 309 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.29

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: rs2031922; hg19: chr10-135340093;