NM_000773.4:c.963C>T

Variant names:

• chr10-133533893-C-T
• rs915909
• NM_000773.4:c.963C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000773.4(CYP2E1):​c.963C>T​(p.Ile321Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,613,912 control chromosomes in the GnomAD database, including 376 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 0.028 (203 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (173 hom.)
• Consequence: CYP2E1 NM_000773.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83
• Publications: 22 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-2.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 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.963C>T	p.Ile321Ile	synonymous	Exon 6 of 9	NP_000764.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.963C>T	p.Ile321Ile	synonymous	Exon 6 of 9	ENSP00000252945.3
	CYP2E1	ENST00000421586.5	TSL:1	c.702C>T	p.Ile234Ile	synonymous	Exon 5 of 8	ENSP00000412754.1
	CYP2E1	ENST00000418356.1	TSL:1	c.552C>T	p.Ile184Ile	synonymous	Exon 4 of 7	ENSP00000397299.1

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4215 AN: 152094 Hom.: 202 Cov.: 33

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00883

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00260 AC: 3807 AN: 1461700 Hom.: 173 Cov.: 31 AF XY: 0.00223 AC XY: 1619 AN XY: 727146

African (AFR) AF: 0.0946 AC: 3165 AN: 33470

American (AMR) AF: 0.00467 AC: 209 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000944 AC: 105 AN: 1111938

Other (OTH) AF: 0.00489 AC: 295 AN: 60386

GnomAD4 genome AF: 0.0278 AC: 4232 AN: 152212 Hom.: 203 Cov.: 33 AF XY: 0.0270 AC XY: 2010 AN XY: 74434

African (AFR) AF: 0.0972 AC: 4034 AN: 41486

American (AMR) AF: 0.00875 AC: 134 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68014

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.0134 Hom.: 215

Bravo AF: 0.0314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.6
PhyloP100		-2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs915909; hg19: chr10-135347397;