11-73975814-ACTT-A

Position:

• chr11-73975814-ACTT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003355.3(UCP2):​c.635-146_635-144delAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,055,832 control chromosomes in the GnomAD database, including 98,236 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (21334 hom., cov: 0)
  • Exomes 𝑓: 0.40 (76902 hom.)
• Consequence: UCP2 NM_003355.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54

Genes affected

UCP2 (HGNC:12518): (uncoupling protein 2) 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. 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 in many tissues, with the greatest expression in skeletal muscle. It is thought to play a role in nonshivering thermogenesis, obesity and diabetes. Chromosomal order is 5'-UCP3-UCP2-3'. [provided by RefSeq, Jul 2008]

UCP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-73975814-ACTT-A is Benign according to our data. Variant chr11-73975814-ACTT-A is described in ClinVar as [Benign]. Clinvar id is 1182647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP2	NM_003355.3	c.635-146_635-144delAAG		intron_variant		ENST00000663595.2	NP_003346.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP2	ENST00000663595.2	c.635-146_635-144delAAG		intron_variant			NM_003355.3	ENSP00000499695.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 76978 AN: 151580 Hom.: 21308 Cov.: 0

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.399 AC: 360361 AN: 904134 Hom.: 76902 AF XY: 0.395 AC XY: 182719 AN XY: 462802

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.508 AC: 77046 AN: 151698 Hom.: 21334 Cov.: 0 AF XY: 0.506 AC XY: 37490 AN XY: 74106

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.459

Alfa AF: 0.468 Hom.: 2162

Bravo AF: 0.520

Asia WGS AF: 0.419 AC: 1455 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs10535527; hg19: chr11-73686859;