rs8192775

Variant names:

• chr10-133534522-G-A
• rs8192775
• NM_000773.4:c.967+625G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-133534522-G-A
• chr10-133534522-G-T

Variant summary

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

The NM_000773.4(CYP2E1):​c.967+625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 152,168 control chromosomes in the GnomAD database, including 809 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 0.090 (809 hom., cov: 33)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 11 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	NM_000773.4	MANE Select	c.967+625G>A		intron	N/A	NP_000764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.967+625G>A		intron	N/A	ENSP00000252945.3
	CYP2E1	ENST00000421586.5	TSL:1	c.706+625G>A		intron	N/A	ENSP00000412754.1
	CYP2E1	ENST00000418356.1	TSL:1	c.556+625G>A		intron	N/A	ENSP00000397299.1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13688 AN: 152048 Hom.: 807 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0900 AC: 13689 AN: 152168 Hom.: 809 Cov.: 33 AF XY: 0.0953 AC XY: 7089 AN XY: 74402

African (AFR) AF: 0.0411 AC: 1707 AN: 41544

American (AMR) AF: 0.117 AC: 1796 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.234 AC: 1206 AN: 5144

South Asian (SAS) AF: 0.186 AC: 895 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1369 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0900 AC: 6116 AN: 67986

Other (OTH) AF: 0.0866 AC: 183 AN: 2112

Alfa AF: 0.0756 Hom.: 688

Bravo AF: 0.0866

Asia WGS AF: 0.167 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.78
PhyloP100		-1.9
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: rs8192775; hg19: chr10-135348026;