10-133526101-G-C

Position:

• chr10-133526101-G-C

Variant summary

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

The XR_946512.3(LOC105378575):​n.243C>G 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 0.0475 in 152,254 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.047 (293 hom., cov: 33)
• Consequence: LOC105378575 XR_946512.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105378575	XR_946512.3	n.243C>G		non_coding_transcript_exon_variant	2/5
LOC105378575	XR_007062396.1	n.859C>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-117-695G>C		intron_variant		5		P1
CYP2E1	ENST00000541261.1	c.-118+460G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7214 AN: 152136 Hom.: 286 Cov.: 33

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0475 AC: 7226 AN: 152254 Hom.: 293 Cov.: 33 AF XY: 0.0491 AC XY: 3659 AN XY: 74464

Gnomad4 AFR AF: 0.0572

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.00975 Hom.: 2

Bravo AF: 0.0565

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.70

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: rs3813867; hg19: chr10-135339605;