10-133527325-G-A

Variant names:

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

Variant summary

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

The ENST00000883804.1(CYP2E1):​c.-71G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,307,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CYP2E1 ENST00000883804.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 0 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: 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=-0.91).

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>A		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>A		5_prime_UTR	Exon 1 of 9	ENSP00000553863.1
	CYP2E1	ENST00000883802.1		c.-71G>A		5_prime_UTR	Exon 1 of 10	ENSP00000553861.1
	CYP2E1	ENST00000883803.1		c.-71G>A		5_prime_UTR	Exon 1 of 9	ENSP00000553862.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1307886 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 644850

African (AFR) AF: 0.00 AC: 0 AN: 29904

American (AMR) AF: 0.00 AC: 0 AN: 33764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20604

East Asian (EAS) AF: 0.00 AC: 0 AN: 38438

South Asian (SAS) AF: 0.0000278 AC: 2 AN: 71990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1015396

Other (OTH) AF: 0.00 AC: 0 AN: 54484

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.46
PromoterAI		-0.038	Neutral

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;