10-133539010-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000773.4(CYP2E1):c.*46A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,498,996 control chromosomes in the GnomAD database, including 435,023 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 0.64 (33578 hom., cov: 31)
  • Exomes 𝑓: 0.77 (401445 hom.)
• Consequence: CYP2E1 NM_000773.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4	c.*46A>G		3_prime_UTR_variant	9/9	ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000252945.8	c.*46A>G		3_prime_UTR_variant	9/9	1	NM_000773.4	P1
CYP2E1	ENST00000368520.1	n.1358+1118A>G		intron_variant, non_coding_transcript_variant		1
CYP2E1	ENST00000463117.6	c.*46A>G		3_prime_UTR_variant	11/11	5		P1
CYP2E1	ENST00000469258.1	n.624A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 96946 AN: 151228 Hom.: 33565 Cov.: 31

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.652

GnomAD3 exomes AF: 0.714 AC: 141380 AN: 197892 Hom.: 51438 AF XY: 0.724 AC XY: 77650 AN XY: 107218

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.675

Gnomad ASJ exome AF: 0.732

Gnomad EAS exome AF: 0.574

Gnomad SAS exome AF: 0.664

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.800

Gnomad OTH exome AF: 0.737

GnomAD4 exome AF: 0.770 AC: 1038024 AN: 1347652 Hom.: 401445 Cov.: 21 AF XY: 0.769 AC XY: 510223 AN XY: 663158

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.789

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.641 AC: 96977 AN: 151344 Hom.: 33578 Cov.: 31 AF XY: 0.639 AC XY: 47285 AN XY: 73948

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.656

Alfa AF: 0.714 Hom.: 6802

Asia WGS AF: 0.624 AC: 2169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.0
Dann	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs2480256; hg19: chr10-135352514; COSMIC: COSV53313530; COSMIC: COSV53313530;