rs8192766

chr10-133525881-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_946512.3(LOC105378575):n.463A>C 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 0.198 in 152,074 control chromosomes in the GnomAD database, including 4,593 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 0.20 (4593 hom., cov: 33)
• Consequence: LOC105378575 XR_946512.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105378575	XR_946512.3	n.463A>C		non_coding_transcript_exon_variant	2/5
LOC105378575	XR_007062396.1	n.943+136A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-117-915T>G		intron_variant		5		P1
CYP2E1	ENST00000541261.1	c.-118+240T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30029 AN: 151956 Hom.: 4569 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.198 AC: 30082 AN: 152074 Hom.: 4593 Cov.: 33 AF XY: 0.200 AC XY: 14884 AN XY: 74366

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.175

Alfa AF: 0.148 Hom.: 280

Asia WGS AF: 0.320 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.2
Dann	Benign	0.80

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: rs8192766; hg19: chr10-135339385;