rs1800849

Positions:

• chr11-74009120-G-A
• chr11-74009120-G-C
• chr11-74009120-G-T

Variant summary

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

The 11-74009120-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,274 control chromosomes in the GnomAD database, including 3,818 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 0.21 (3809 hom., cov: 32)
  • Exomes 𝑓: 0.24 (9 hom.)
• Consequence: UCP3 NM_003356.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

UCP3 (HGNC:12519): (uncoupling protein 3) 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. The different UCPs have tissue-specific expression; this gene is primarily expressed in skeletal muscle. This gene's protein product is postulated to protect mitochondria against lipid-induced oxidative stress. Expression levels of this gene increase when fatty acid supplies to mitochondria exceed their oxidation capacity and the protein enables the export of fatty acids from mitochondria. UCPs contain the three solcar protein domains typically found in MACPs. Two splice variants have been found for this gene.[provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP3	NM_003356.4			upstream_gene_variant		ENST00000314032.9	NP_003347.1
UCP3	NM_022803.3			upstream_gene_variant			NP_073714.1
UCP3	XM_047427519.1			upstream_gene_variant			XP_047283475.1
UCP3	XR_007062495.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9			upstream_gene_variant		1	NM_003356.4	ENSP00000323740	P1
UCP3	ENST00000426995.2			upstream_gene_variant		1		ENSP00000392143

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32299 AN: 151966 Hom.: 3811 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.237 AC: 45 AN: 190 Hom.: 9 Cov.: 0 AF XY: 0.214 AC XY: 24 AN XY: 112

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.212 AC: 32297 AN: 152084 Hom.: 3809 Cov.: 32 AF XY: 0.218 AC XY: 16170 AN XY: 74326

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.177

Alfa AF: 0.218 Hom.: 2421

Bravo AF: 0.189

Asia WGS AF: 0.259 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.52

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: rs1800849; hg19: chr11-73720165;