11-73980729-T-C

Position:

• chr11-73980729-T-C

Variant summary

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

The NM_001381943.1(UCP2):​c.-157A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,302 control chromosomes in the GnomAD database, including 851 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 0.085 (851 hom., cov: 32)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: UCP2 NM_001381943.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

Genes affected

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 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP2	NM_003355.3	c.-100+747A>G		intron_variant		ENST00000663595.2	NP_003346.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP2	ENST00000663595.2	c.-100+747A>G		intron_variant			NM_003355.3	ENSP00000499695.1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12838 AN: 152148 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0440

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0928

GnomAD4 exome AF: 0.0556 AC: 2 AN: 36 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 2 AN XY: 28

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0357

GnomAD4 genome AF: 0.0845 AC: 12869 AN: 152266 Hom.: 851 Cov.: 32 AF XY: 0.0822 AC XY: 6118 AN XY: 74464

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0660

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0438

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0580 Hom.: 461

Bravo AF: 0.0931

Asia WGS AF: 0.0330 AC: 113 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	5.7
DANN	Benign	0.68

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: rs17132534; hg19: chr11-73691774;