10-133524462-C-T

Variant names:

• chr10-133524462-C-T
• rs9418990
• ENST00000463117.6:c.-117-2334C>T

Variant summary

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

The XR_946512.3(LOC105378575):​n.1882G>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 0.631 in 151,994 control chromosomes in the GnomAD database, including 35,548 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 0.63 (35548 hom., cov: 33)
• Consequence: LOC105378575 XR_946512.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 11 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]

LOC105378575 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000463117.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000463117.6	TSL:5	c.-117-2334C>T		intron	N/A	ENSP00000440689.1	P05181
	ENSG00000278518	ENST00000822676.1		n.230+2298G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95963 AN: 151876 Hom.: 35532 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.646

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.631 AC: 95984 AN: 151994 Hom.: 35548 Cov.: 33 AF XY: 0.633 AC XY: 47000 AN XY: 74304

African (AFR) AF: 0.212 AC: 8761 AN: 41394

American (AMR) AF: 0.681 AC: 10396 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2410 AN: 3464

East Asian (EAS) AF: 0.570 AC: 2946 AN: 5170

South Asian (SAS) AF: 0.647 AC: 3114 AN: 4816

European-Finnish (FIN) AF: 0.870 AC: 9222 AN: 10598

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56764 AN: 67958

Other (OTH) AF: 0.650 AC: 1375 AN: 2114

Alfa AF: 0.781 Hom.: 27172

Asia WGS AF: 0.614 AC: 2130 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		-0.19
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: rs9418990; hg19: chr10-135337966;