chr10-133539010-A-G

Variant names:

• chr10-133539010-A-G
• rs2480256
• NM_000773.4:c.*46A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 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=-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 rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.*46A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.*46A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_000773.4	ENSP00000252945.3

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

GnomAD2 exomes AF: 0.714 AC: 141380 AN: 197892 AF XY: 0.724

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 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

African (AFR) AF: 0.320 AC: 9531 AN: 29822

American (AMR) AF: 0.679 AC: 20416 AN: 30074

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 16213 AN: 22052

East Asian (EAS) AF: 0.563 AC: 21173 AN: 37638

South Asian (SAS) AF: 0.663 AC: 46023 AN: 69386

European-Finnish (FIN) AF: 0.789 AC: 40097 AN: 50830

Middle Eastern (MID) AF: 0.702 AC: 3761 AN: 5358

European-Non Finnish (NFE) AF: 0.802 AC: 840059 AN: 1047080

Other (OTH) AF: 0.735 AC: 40751 AN: 55412

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

African (AFR) AF: 0.324 AC: 13363 AN: 41240

American (AMR) AF: 0.678 AC: 10317 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2524 AN: 3458

East Asian (EAS) AF: 0.567 AC: 2911 AN: 5134

South Asian (SAS) AF: 0.644 AC: 3098 AN: 4812

European-Finnish (FIN) AF: 0.789 AC: 8254 AN: 10462

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.800 AC: 54161 AN: 67730

Other (OTH) AF: 0.656 AC: 1373 AN: 2094

Alfa AF: 0.703 Hom.: 6845

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
PhyloP100		0.28
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: rs2480256; hg19: chr10-135352514; COSMIC: COSV53313530; COSMIC: COSV53313530;