XR_007062396.1:n.5527C>T

Variant names:

• chr10-133520838-G-A
• rs10776687
• XR_007062396.1:n.5527C>T

Variant summary

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

The XR_007062396.1(LOC105378575):​n.5527C>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 0.0451 in 152,106 control chromosomes in the GnomAD database, including 279 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 0.045 (279 hom., cov: 33)
• Consequence: LOC105378575 XR_007062396.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• 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]

SCART1 (HGNC:32411): (scavenger receptor family member expressed on T cells 1) Predicted to enable scavenger receptor activity. Predicted to be involved in endocytosis. Located in brush border and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000463117.6	TSL:5	c.-118+278G>A		intron	N/A	ENSP00000440689.1
	SCART1	ENST00000488261.6	TSL:2	n.4422-2433G>A		intron	N/A
	ENSG00000278518	ENST00000822676.1		n.230+5922C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6849 AN: 151988 Hom.: 273 Cov.: 33

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0451 AC: 6858 AN: 152106 Hom.: 279 Cov.: 33 AF XY: 0.0468 AC XY: 3483 AN XY: 74348

African (AFR) AF: 0.0491 AC: 2037 AN: 41472

American (AMR) AF: 0.0909 AC: 1390 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 180 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1049 AN: 5152

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4814

European-Finnish (FIN) AF: 0.0219 AC: 231 AN: 10570

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0264 AC: 1795 AN: 68008

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

Alfa AF: 0.0384 Hom.: 199

Bravo AF: 0.0538

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		-0.21
PromoterAI		-0.030	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: rs10776687; hg19: chr10-135334342;