10-133528530-G-T

Variant names:

• chr10-133528530-G-T
• rs72559710
• NM_000773.4:c.227G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000773.4(CYP2E1):​c.227G>T​(p.Arg76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CYP2E1 NM_000773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 31 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.227G>T	p.Arg76Leu	missense_variant	Exon 2 of 9	ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.227G>T	p.Arg76Leu	missense_variant	Exon 2 of 9	1	NM_000773.4	ENSP00000252945.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250672 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.55	.;T;T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.3	L;.;L
PhyloP100		1.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.4	N;D;N
REVEL	Benign	0.21
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.021	D;T;D
Polyphen		1.0	D;.;D
Vest4		0.54
MutPred		0.67		Loss of catalytic residue at R76 (P = 0.0274);Loss of catalytic residue at R76 (P = 0.0274);Loss of catalytic residue at R76 (P = 0.0274);
MVP		0.72
MPC		1.1
ClinPred		0.60	D
GERP RS		3.0
Varity_R		0.50
gMVP		0.63
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs72559710; hg19: chr10-135342034;