chr10-133533423-C-A

Variant names:

• chr10-133533423-C-A
• rs915907
• NM_000773.4:c.826-333C>A

Variant summary

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

The NM_000773.4(CYP2E1):​c.826-333C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,134 control chromosomes in the GnomAD database, including 2,652 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 0.18 (2652 hom., cov: 33)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 12 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 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.826-333C>A		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.826-333C>A		intron	N/A	ENSP00000252945.3	P05181
	CYP2E1	ENST00000421586.5	TSL:1	c.565-333C>A		intron	N/A	ENSP00000412754.1	H0Y7H4
	CYP2E1	ENST00000418356.1	TSL:1	c.415-333C>A		intron	N/A	ENSP00000397299.1	H0Y593

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26943 AN: 152016 Hom.: 2654 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.177 AC: 26951 AN: 152134 Hom.: 2652 Cov.: 33 AF XY: 0.184 AC XY: 13677 AN XY: 74364

African (AFR) AF: 0.151 AC: 6278 AN: 41490

American (AMR) AF: 0.213 AC: 3262 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2208 AN: 5164

South Asian (SAS) AF: 0.298 AC: 1439 AN: 4824

European-Finnish (FIN) AF: 0.219 AC: 2322 AN: 10588

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10509 AN: 67990

Other (OTH) AF: 0.160 AC: 337 AN: 2112

Alfa AF: 0.162 Hom.: 3431

Bravo AF: 0.174

Asia WGS AF: 0.316 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.3
DANN	Benign	0.91
PhyloP100		-0.047
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: rs915907; hg19: chr10-135346927;