rs10776687

Positions:

• chr10-133520838-G-A

Variant summary

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

The XR_946512.3(LOC105378575):​n.5506C>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_946512.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105378575	XR_946512.3	n.5506C>T		non_coding_transcript_exon_variant	2/5
LOC105378575	XR_007062396.1	n.5527C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-118+278G>A		intron_variant		5		ENSP00000440689	P1
SCART1	ENST00000488261.6	n.4422-2433G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0491

Gnomad4 AMR AF: 0.0909

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0264

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0370 Hom.: 151

Bravo AF: 0.0538

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.71

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: rs10776687; hg19: chr10-135334342;