ENST00000660751.1:n.261C>T

Variant names:

• chr11-73983709-C-T
• rs659366
• ENST00000660751.1:n.261C>T

Variant summary

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

The ENST00000660751.1(ENSG00000287425):​n.261C>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 0.4 in 152,158 control chromosomes in the GnomAD database, including 12,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.40 (12224 hom., cov: 33)
• Consequence: ENSG00000287425 ENST00000660751.1 non_coding_transcript_exon
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0280
• Publications: 302 publications found

Genes affected

ENSG00000287425 (HGNC:):

UCP2 (HGNC:12518): (uncoupling protein 2) Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. This gene is expressed in many tissues, with the greatest expression in skeletal muscle. It is thought to play a role in nonshivering thermogenesis, obesity and diabetes. Chromosomal order is 5'-UCP3-UCP2-3'. [provided by RefSeq, Jul 2008]

UCP2 Gene-Disease associations (from GenCC):

• hyperinsulinism due to UCP2 deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000660751.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000287425	ENST00000660751.1		n.261C>T		non_coding_transcript_exon	Exon 1 of 1
	UCP2	ENST00000952750.1		c.-682G>A		upstream_gene	N/A	ENSP00000622809.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60896 AN: 152040 Hom.: 12223 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.400 AC: 60914 AN: 152158 Hom.: 12224 Cov.: 33 AF XY: 0.401 AC XY: 29808 AN XY: 74366

African (AFR) AF: 0.453 AC: 18805 AN: 41508

American (AMR) AF: 0.428 AC: 6536 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1071 AN: 3472

East Asian (EAS) AF: 0.426 AC: 2205 AN: 5172

South Asian (SAS) AF: 0.346 AC: 1666 AN: 4820

European-Finnish (FIN) AF: 0.398 AC: 4219 AN: 10588

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25303 AN: 67998

Other (OTH) AF: 0.372 AC: 786 AN: 2114

Alfa AF: 0.379 Hom.: 48775

Bravo AF: 0.406

Asia WGS AF: 0.387 AC: 1343 AN: 3478

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		-0.028

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs659366; hg19: chr11-73694754;