rs2480256

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-133539010-A-C
• chr10-133539010-A-G
• chr10-133539010-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000252945.8(CYP2E1):​c.*46A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2E1 ENST00000252945.8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252945.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	NM_000773.4	MANE Select	c.*46A>C		3_prime_UTR	Exon 9 of 9	NP_000764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.*46A>C		3_prime_UTR	Exon 9 of 9	ENSP00000252945.3
	CYP2E1	ENST00000368520.1	TSL:1	n.1358+1118A>C		intron	N/A
	CYP2E1	ENST00000469258.1	TSL:2	n.624A>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1349812 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 664176

African (AFR) AF: 0.00 AC: 0 AN: 29982

American (AMR) AF: 0.00 AC: 0 AN: 30148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22102

East Asian (EAS) AF: 0.00 AC: 0 AN: 37676

South Asian (SAS) AF: 0.00 AC: 0 AN: 69574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048614

Other (OTH) AF: 0.00 AC: 0 AN: 55498

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 6845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.26
PhyloP100		0.28

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;