10-133527325-G-T

Variant names:

• chr10-133527325-G-T
• rs6413420
• ENST00000883804.1:c.-71G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000883804.1(CYP2E1):​c.-71G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,457,132 control chromosomes in the GnomAD database, including 2,163 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 0.039 (150 hom., cov: 34)
  • Exomes 𝑓: 0.051 (2013 hom.)
• Consequence: CYP2E1 ENST00000883804.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 37 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]

ENSG00000278518 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000883804.1. 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.-71G>T		upstream_gene	N/A	NP_000764.1	P05181

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000883804.1		c.-71G>T		5_prime_UTR	Exon 1 of 9	ENSP00000553863.1
	CYP2E1	ENST00000883802.1		c.-71G>T		5_prime_UTR	Exon 1 of 10	ENSP00000553861.1
	CYP2E1	ENST00000883803.1		c.-71G>T		5_prime_UTR	Exon 1 of 9	ENSP00000553862.1

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5907 AN: 149802 Hom.: 150 Cov.: 34

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0353

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.00342

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0494

GnomAD4 exome AF: 0.0511 AC: 66804 AN: 1307210 Hom.: 2013 Cov.: 19 AF XY: 0.0516 AC XY: 33246 AN XY: 644540

African (AFR) AF: 0.0155 AC: 463 AN: 29900

American (AMR) AF: 0.0264 AC: 892 AN: 33762

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 1549 AN: 20594

East Asian (EAS) AF: 0.000702 AC: 27 AN: 38438

South Asian (SAS) AF: 0.0664 AC: 4779 AN: 71944

European-Finnish (FIN) AF: 0.0304 AC: 1205 AN: 39652

Middle Eastern (MID) AF: 0.0798 AC: 291 AN: 3648

European-Non Finnish (NFE) AF: 0.0540 AC: 54752 AN: 1014824

Other (OTH) AF: 0.0523 AC: 2846 AN: 54448

GnomAD4 genome AF: 0.0395 AC: 5915 AN: 149922 Hom.: 150 Cov.: 34 AF XY: 0.0394 AC XY: 2882 AN XY: 73070

African (AFR) AF: 0.0174 AC: 707 AN: 40672

American (AMR) AF: 0.0354 AC: 529 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.0770 AC: 266 AN: 3456

East Asian (EAS) AF: 0.00343 AC: 17 AN: 4962

South Asian (SAS) AF: 0.0733 AC: 339 AN: 4624

European-Finnish (FIN) AF: 0.0262 AC: 272 AN: 10384

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0537 AC: 3628 AN: 67594

Other (OTH) AF: 0.0488 AC: 101 AN: 2068

Alfa AF: 0.0508 Hom.: 555

Bravo AF: 0.0373

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-0.46
PromoterAI		-0.053	Neutral
Mutation Taster		=100/0	polymorphism

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: rs6413420; hg19: chr10-135340829;