4-140563611-AT-A

Position:

• chr4-140563611-AT-A

Variant summary

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

The NM_021833.5(UCP1):​c.326-94delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 940,278 control chromosomes in the GnomAD database, including 948 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (598 hom., cov: 0)
  • Exomes 𝑓: 0.20 (350 hom.)
• Consequence: UCP1 NM_021833.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.439

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 -10 ACMG points.

• BP6: Variant 4-140563611-AT-A is Benign according to our data. Variant chr4-140563611-AT-A is described in ClinVar as [Benign]. Clinvar id is 1227025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP1	NM_021833.5	c.326-94delA		intron_variant		ENST00000262999.4	NP_068605.1
UCP1	XM_005263206.4	c.326-97delA		intron_variant			XP_005263263.1
UCP1	XM_011532228.3	c.326-94delA		intron_variant			XP_011530530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP1	ENST00000262999.4	c.326-94delA		intron_variant		1	NM_021833.5	ENSP00000262999.3

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 13695 AN: 144098 Hom.: 598 Cov.: 0

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0805

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.0968

GnomAD4 exome AF: 0.202 AC: 161068 AN: 796128 Hom.: 350 AF XY: 0.205 AC XY: 82459 AN XY: 402814

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.0951 AC: 13705 AN: 144150 Hom.: 598 Cov.: 0 AF XY: 0.0972 AC XY: 6795 AN XY: 69880

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.0860

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0836

Gnomad4 OTH AF: 0.0960

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: rs112019388; hg19: chr4-141484765;