chr4-140568842-T-G

Variant names:

• chr4-140568842-T-G
• rs10011540
• NM_021833.5:c.-113A>C

Variant summary

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

The NM_021833.5(UCP1):​c.-113A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,501,780 control chromosomes in the GnomAD database, including 6,550 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 0.10 (892 hom., cov: 32)
  • Exomes 𝑓: 0.088 (5658 hom.)
• Consequence: UCP1 NM_021833.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCP1	NM_021833.5	c.-113A>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000262999.4	NP_068605.1
UCP1	XM_005263206.4	c.-113A>C		5_prime_UTR_variant	Exon 1 of 6		XP_005263263.1
UCP1	XM_011532228.3	c.-113A>C		5_prime_UTR_variant	Exon 1 of 6		XP_011530530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCP1	ENST00000262999.4	c.-113A>C		5_prime_UTR_variant	Exon 1 of 6	1	NM_021833.5	ENSP00000262999.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15654 AN: 152106 Hom.: 891 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0783

Gnomad OTH AF: 0.0890

GnomAD4 exome AF: 0.0877 AC: 118305 AN: 1349556 Hom.: 5658 Cov.: 25 AF XY: 0.0894 AC XY: 59377 AN XY: 664530

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.0901

Gnomad4 EAS exome AF: 0.0737

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0877

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.0881

GnomAD4 genome AF: 0.103 AC: 15681 AN: 152224 Hom.: 892 Cov.: 32 AF XY: 0.104 AC XY: 7744 AN XY: 74434

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.0701

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0838

Gnomad4 NFE AF: 0.0783

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0820 Hom.: 575

Bravo AF: 0.103

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10011540; hg19: chr4-141489996;