10-133528756-C-T

Variant names:

• chr10-133528756-C-T
• rs943975
• NM_000773.4:c.337+116C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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 -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.

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.337+116C>T		intron	N/A	NP_000764.1	P05181

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.337+116C>T		intron	N/A	ENSP00000252945.3	P05181
	CYP2E1	ENST00000421586.5	TSL:1	c.76+1184C>T		intron	N/A	ENSP00000412754.1	H0Y7H4
	CYP2E1	ENST00000418356.1	TSL:1	c.76+1184C>T		intron	N/A	ENSP00000397299.1	H0Y593

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

African (AFR) AF: 0.516 AC: 13516 AN: 26218

American (AMR) AF: 0.813 AC: 25027 AN: 30768

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 17227 AN: 19668

East Asian (EAS) AF: 0.788 AC: 27240 AN: 34554

South Asian (SAS) AF: 0.955 AC: 63138 AN: 66132

European-Finnish (FIN) AF: 0.934 AC: 42405 AN: 45420

Middle Eastern (MID) AF: 0.878 AC: 2977 AN: 3392

European-Non Finnish (NFE) AF: 0.922 AC: 792288 AN: 859278

Other (OTH) AF: 0.879 AC: 42627 AN: 48474

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

African (AFR) AF: 0.521 AC: 21641 AN: 41502

American (AMR) AF: 0.822 AC: 12571 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3043 AN: 3470

East Asian (EAS) AF: 0.797 AC: 4110 AN: 5160

South Asian (SAS) AF: 0.958 AC: 4626 AN: 4830

European-Finnish (FIN) AF: 0.942 AC: 10003 AN: 10622

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62634 AN: 68020

Other (OTH) AF: 0.823 AC: 1739 AN: 2114

Alfa AF: 0.883 Hom.: 102312

Asia WGS AF: 0.891 AC: 3098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.90
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs943975; hg19: chr10-135342260;