rs12502572

chr4-140563980-G-Achr4-140563980-G-C

Variant summary

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

The NM_021833.5(UCP1):c.326-462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,970 control chromosomes in the GnomAD database, including 17,040 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 0.45 (17040 hom., cov: 32)
• Consequence: UCP1 NM_021833.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

UCP1 (HGNC:12517): (uncoupling protein 1) Mitochondrial uncoupling proteins (UCP) are members of the 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 only in brown adipose tissue, a specialized tissue which functions to produce heat. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCP1	NM_021833.5	c.326-462C>T		intron_variant		ENST00000262999.4
UCP1	XM_005263206.4	c.326-465C>T		intron_variant
UCP1	XM_011532228.3	c.326-462C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP1	ENST00000262999.4	c.326-462C>T		intron_variant		1	NM_021833.5	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67670 AN: 151850 Hom.: 17011 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.446 AC: 67755 AN: 151970 Hom.: 17040 Cov.: 32 AF XY: 0.450 AC XY: 33432 AN XY: 74270

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.430

Alfa AF: 0.280 Hom.: 1006

Bravo AF: 0.463

Asia WGS AF: 0.518 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.20
Dann	Benign	0.37

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: rs12502572; hg19: chr4-141485134;