rs12502572

Variant names:

• chr4-140563980-G-A
• rs12502572
• NM_021833.5:c.326-462C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-140563980-G-A
• chr4-140563980-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021833.5. 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
	UCP1	NM_021833.5	MANE Select	c.326-462C>T		intron	N/A	NP_068605.1	P25874
	UCP1	NM_001440546.1		c.326-465C>T		intron	N/A	NP_001427475.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP1	ENST00000262999.4	TSL:1 MANE Select	c.326-462C>T		intron	N/A	ENSP00000262999.3	P25874
	UCP1	ENST00000956211.1		c.326-465C>T		intron	N/A	ENSP00000626270.1

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

African (AFR) AF: 0.690 AC: 28600 AN: 41468

American (AMR) AF: 0.439 AC: 6715 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3468

East Asian (EAS) AF: 0.508 AC: 2614 AN: 5150

South Asian (SAS) AF: 0.488 AC: 2350 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3617 AN: 10530

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21247 AN: 67934

Other (OTH) AF: 0.430 AC: 906 AN: 2106

Alfa AF: 0.297 Hom.: 1197

Bravo AF: 0.463

Asia WGS AF: 0.518 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.37
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs12502572; hg19: chr4-141485134;