rs8192772

Variant names:

• chr10-133531207-T-C
• rs8192772
• NM_000773.4:c.338-378T>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.338-378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,128 control chromosomes in the GnomAD database, including 920 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 0.10 (920 hom., cov: 33)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.338-378T>C		intron_variant	Intron 2 of 8	ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.338-378T>C		intron_variant	Intron 2 of 8	1	NM_000773.4	ENSP00000252945.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15656 AN: 152010 Hom.: 927 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.103 AC: 15644 AN: 152128 Hom.: 920 Cov.: 33 AF XY: 0.107 AC XY: 7982 AN XY: 74374

African (AFR) AF: 0.123 AC: 5110 AN: 41446

American (AMR) AF: 0.101 AC: 1537 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1203 AN: 5178

South Asian (SAS) AF: 0.248 AC: 1196 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1246 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0710 AC: 4826 AN: 68008

Other (OTH) AF: 0.0995 AC: 210 AN: 2110

Alfa AF: 0.0817 Hom.: 1290

Bravo AF: 0.0990

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.80
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: rs8192772; hg19: chr10-135344711;