10-133533893-C-T

Position:

• chr10-133533893-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

CYP2E1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.963C>T	p.Ile321Ile	synonymous_variant	6/9	ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.963C>T	p.Ile321Ile	synonymous_variant	6/9	1	NM_000773.4	ENSP00000252945.3

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

Gnomad4 AFR exome AF: 0.0946

Gnomad4 AMR exome AF: 0.00467

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000944

Gnomad4 OTH exome AF: 0.00489

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

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.00875

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.00743 Hom.: 68

Bravo AF: 0.0314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs915909; hg19: chr10-135347397;