11-73975136-T-A

Variant names:

• chr11-73975136-T-A
• rs116537211
• NM_003355.3:c.816-15A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003355.3(UCP2):​c.816-15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,601,194 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: UCP2 NM_003355.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hyperinsulinism due to UCP2 deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 11-73975136-T-A is Benign according to our data. Variant chr11-73975136-T-A is described in ClinVar as [Benign]. Clinvar id is 1990457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 117 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCP2	NM_003355.3	c.816-15A>T		intron_variant	Intron 7 of 7	ENST00000663595.2	NP_003346.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCP2	ENST00000663595.2	c.816-15A>T		intron_variant	Intron 7 of 7		NM_003355.3	ENSP00000499695.1
UCP2	ENST00000310473.10	c.816-15A>T		intron_variant	Intron 8 of 8	1		ENSP00000312029.3
UCP2	ENST00000536983.5	c.635-15A>T		intron_variant	Intron 6 of 6	5		ENSP00000441147.1
UCP2	ENST00000544615.5	n.735-15A>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.000778 AC: 118 AN: 151632 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000317 AC: 73 AN: 230594 AF XY: 0.000273

Gnomad AFR exome AF: 0.00293

Gnomad AMR exome AF: 0.000340

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000175

Gnomad OTH exome AF: 0.000345

GnomAD4 exome AF: 0.000249 AC: 361 AN: 1449444 Hom.: 2 Cov.: 30 AF XY: 0.000253 AC XY: 182 AN XY: 720454

African (AFR) AF: 0.00312 AC: 103 AN: 33022

American (AMR) AF: 0.000395 AC: 17 AN: 43046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 38966

South Asian (SAS) AF: 0.00 AC: 0 AN: 84692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52814

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5758

European-Non Finnish (NFE) AF: 0.000176 AC: 195 AN: 1105238

Other (OTH) AF: 0.000651 AC: 39 AN: 59946

GnomAD4 genome AF: 0.000771 AC: 117 AN: 151750 Hom.: 0 Cov.: 32 AF XY: 0.000822 AC XY: 61 AN XY: 74190

African (AFR) AF: 0.00237 AC: 98 AN: 41316

American (AMR) AF: 0.000197 AC: 3 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67922

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.000470 Hom.: 0

Bravo AF: 0.00103

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 04, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.6
DANN	Benign	0.81
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs116537211; hg19: chr11-73686181;