rs2070673

chr10-133527063-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000622716.1(ENSG00000278518):n.451T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 304,230 control chromosomes in the GnomAD database, including 83,504 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 0.67 (38112 hom., cov: 33)
  • Exomes 𝑓: 0.77 (45392 hom.)
• Consequence: ENST00000622716.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

Genes affected

(HGNC:):

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000622716.1	n.451T>A		non_coding_transcript_exon_variant	1/1
CYP2E1	ENST00000463117.6	c.-40+190A>T		intron_variant		5		P1
CYP2E1	ENST00000541261.1	c.-40+190A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102273 AN: 151858 Hom.: 38095 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.768 AC: 116879 AN: 152254 Hom.: 45392 Cov.: 4 AF XY: 0.769 AC XY: 58802 AN XY: 76452

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.685

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.865

Gnomad4 NFE exome AF: 0.826

Gnomad4 OTH exome AF: 0.736

GnomAD4 genome AF: 0.673 AC: 102311 AN: 151976 Hom.: 38112 Cov.: 33 AF XY: 0.674 AC XY: 50066 AN XY: 74302

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.695

Alfa AF: 0.737 Hom.: 4831

Asia WGS AF: 0.626 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.0
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070673; hg19: chr10-135340567;