rs1800849

Variant names:

• chr11-74009120-G-A
• rs1800849
• ENST00000756620.1:n.419+4103G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000756620.1(ENSG00000298570):​n.419+4103G>A variant causes a intron 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: ENSG00000298570 ENST00000756620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 167 publications found

Genes affected

ENSG00000298570 (HGNC:):

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000756620.1. 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
	UCP3	NM_003356.4	MANE Select	c.-238C>T		upstream_gene	N/A	NP_003347.1	P55916-1
	UCP3	NM_022803.3		c.-238C>T		upstream_gene	N/A	NP_073714.1	P55916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000298570	ENST00000756620.1		n.419+4103G>A		intron	N/A
	UCP3	ENST00000314032.9	TSL:1 MANE Select	c.-238C>T		upstream_gene	N/A	ENSP00000323740.4	P55916-1
	UCP3	ENST00000426995.2	TSL:1	c.-238C>T		upstream_gene	N/A	ENSP00000392143.2	P55916-2

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

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.286 AC: 4 AN: 14

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.350 AC: 7 AN: 20

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.203 AC: 24 AN: 118

Other (OTH) AF: 0.250 AC: 5 AN: 20

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

African (AFR) AF: 0.130 AC: 5383 AN: 41512

American (AMR) AF: 0.152 AC: 2328 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1565 AN: 5156

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4014 AN: 10562

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16569 AN: 67956

Other (OTH) AF: 0.177 AC: 374 AN: 2112

Alfa AF: 0.225 Hom.: 4054

Bravo AF: 0.189

Asia WGS AF: 0.259 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.52
PhyloP100		-0.17
PromoterAI		0.061	Neutral
Mutation Taster		=300/0	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: rs1800849; hg19: chr11-73720165;