chr10-133537633-G-C

Variant names:

• chr10-133537633-G-C
• rs2070676
• NM_000773.4:c.1156-118G>C

Variant summary

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

The NM_000773.4(CYP2E1):​c.1156-118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 902,148 control chromosomes in the GnomAD database, including 324,270 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 0.74 (44458 hom., cov: 33)
  • Exomes 𝑓: 0.86 (279812 hom.)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 58 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	NM_000773.4	MANE Select	c.1156-118G>C		intron	N/A	NP_000764.1	P05181

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.1156-118G>C		intron	N/A	ENSP00000252945.3	P05181
	CYP2E1	ENST00000421586.5	TSL:1	c.895-118G>C		intron	N/A	ENSP00000412754.1	H0Y7H4
	CYP2E1	ENST00000418356.1	TSL:1	c.745-118G>C		intron	N/A	ENSP00000397299.1	H0Y593

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111630 AN: 151794 Hom.: 44438 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.747

GnomAD4 exome AF: 0.862 AC: 646615 AN: 750236 Hom.: 279812 Cov.: 10 AF XY: 0.862 AC XY: 331611 AN XY: 384482

African (AFR) AF: 0.366 AC: 7014 AN: 19160

American (AMR) AF: 0.819 AC: 18509 AN: 22592

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 12960 AN: 15704

East Asian (EAS) AF: 0.831 AC: 28935 AN: 34804

South Asian (SAS) AF: 0.845 AC: 43485 AN: 51474

European-Finnish (FIN) AF: 0.914 AC: 36293 AN: 39696

Middle Eastern (MID) AF: 0.764 AC: 2882 AN: 3774

European-Non Finnish (NFE) AF: 0.885 AC: 466689 AN: 527110

Other (OTH) AF: 0.831 AC: 29848 AN: 35922

GnomAD4 genome AF: 0.735 AC: 111685 AN: 151912 Hom.: 44458 Cov.: 33 AF XY: 0.739 AC XY: 54905 AN XY: 74268

African (AFR) AF: 0.375 AC: 15481 AN: 41230

American (AMR) AF: 0.800 AC: 12227 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2866 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4253 AN: 5182

South Asian (SAS) AF: 0.830 AC: 3995 AN: 4814

European-Finnish (FIN) AF: 0.923 AC: 9792 AN: 10608

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60419 AN: 68012

Other (OTH) AF: 0.750 AC: 1583 AN: 2112

Alfa AF: 0.713 Hom.: 2147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.021
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: rs2070676; hg19: chr10-135351137;