10-133537858-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BA1

The NM_000773.4(CYP2E1):c.1263C>T(p.Phe421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,612,742 control chromosomes in the GnomAD database, including 22,115 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (7973 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14142 hom.)
• Consequence: CYP2E1 NM_000773.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.107

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

Verdict is Benign. Variant got -11 ACMG points.

• BP6: Variant 10-133537858-C-T is Benign according to our data. Variant chr10-133537858-C-T is described in ClinVar as [Benign]. Clinvar id is 768403.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.107 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4	c.1263C>T	p.Phe421=	synonymous_variant	8/9	ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000252945.8	c.1263C>T	p.Phe421=	synonymous_variant	8/9	1	NM_000773.4	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39082 AN: 151696 Hom.: 7950 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.0717

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.127 AC: 185075 AN: 1460928 Hom.: 14142 Cov.: 32 AF XY: 0.126 AC XY: 91630 AN XY: 726738

Gnomad4 AFR exome AF: 0.609

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.0838

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.258 AC: 39144 AN: 151814 Hom.: 7973 Cov.: 32 AF XY: 0.254 AC XY: 18852 AN XY: 74244

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0766

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.245

Alfa AF: 0.139 Hom.: 3922

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2515641; hg19: chr10-135351362;