rs3813866

Variant names:

• chr10-133525830-T-A
• rs3813866
• XR_946512.3:n.514A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133525830-T-A
• chr10-133525830-T-C

Variant summary

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

The XR_946512.3(LOC105378575):​n.514A>T 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 0.111 in 152,078 control chromosomes in the GnomAD database, including 1,303 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 0.11 (1303 hom., cov: 33)
• Consequence: LOC105378575 XR_946512.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 5 publications found

Genes affected

LOC105378575 (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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378575	XR_946512.3	n.514A>T		non_coding_transcript_exon_variant	Exon 2 of 5
LOC105378575	XR_007062396.1	n.943+187A>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-117-966T>A		intron_variant	Intron 1 of 10	5		ENSP00000440689.1
CYP2E1	ENST00000541261.1	c.-118+189T>A		intron_variant	Intron 1 of 3	4		ENSP00000437799.1
ENSG00000278518	ENST00000822676.1	n.230+930A>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16783 AN: 151960 Hom.: 1294 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.111 AC: 16821 AN: 152078 Hom.: 1303 Cov.: 33 AF XY: 0.110 AC XY: 8167 AN XY: 74356

African (AFR) AF: 0.230 AC: 9520 AN: 41450

American (AMR) AF: 0.126 AC: 1929 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5166

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4826

European-Finnish (FIN) AF: 0.0282 AC: 299 AN: 10618

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0498 AC: 3382 AN: 67950

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0329 Hom.: 13

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.58
PhyloP100		0.076
PromoterAI		0.0033	Neutral
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: rs3813866; hg19: chr10-135339334;