rs3813866

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LOC105378575	XR_946512.3	n.514A>T		non_coding_transcript_exon_variant	2/5
LOC105378575	XR_007062396.1	n.943+187A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-117-966T>A		intron_variant		5		ENSP00000440689	P1
CYP2E1	ENST00000541261.1	c.-118+189T>A		intron_variant		4		ENSP00000437799

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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0282

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.0938

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3813866; hg19: chr10-135339334;