chr10-133528756-C-T

Position:

• chr10-133528756-C-T

Variant summary

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

The NM_000773.4(CYP2E1):​c.337+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 1,286,124 control chromosomes in the GnomAD database, including 516,439 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 0.80 (50516 hom., cov: 37)
  • Exomes 𝑓: 0.91 (465923 hom.)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.337+116C>T		intron_variant		ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.337+116C>T		intron_variant		1	NM_000773.4	ENSP00000252945.3

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121418 AN: 152102 Hom.: 50493 Cov.: 37

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.821

GnomAD4 exome AF: 0.905 AC: 1026445 AN: 1133904 Hom.: 465923 AF XY: 0.909 AC XY: 510180 AN XY: 561520

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.813

Gnomad4 ASJ exome AF: 0.876

Gnomad4 EAS exome AF: 0.788

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.934

Gnomad4 NFE exome AF: 0.922

Gnomad4 OTH exome AF: 0.879

GnomAD4 genome AF: 0.798 AC: 121482 AN: 152220 Hom.: 50516 Cov.: 37 AF XY: 0.801 AC XY: 59603 AN XY: 74436

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.823

Alfa AF: 0.898 Hom.: 69682

Asia WGS AF: 0.891 AC: 3098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.90

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: rs943975; hg19: chr10-135342260;