dbSNP rs201691196: UCP2:c.816-10T>G (chr11-73975131-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003355.3(UCP2):c.816-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,606,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

UCP2
NM_003355.3 intron

Scores

Splicing: ADA: 0.8323

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.25

Publications

0 publications found

Variant links:

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

UCP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-73975131-A-C is Benign according to our data. Variant chr11-73975131-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 757102.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003355.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UCP2	NM_003355.3	MANE Select	c.816-10T>G	intron	N/A	NP_003346.2
UCP2	NM_001381943.1		c.816-10T>G	intron	N/A	NP_001368872.1	P55851
UCP2	NM_001381944.1		c.816-10T>G	intron	N/A	NP_001368873.1	P55851

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UCP2	ENST00000663595.2	MANE Select	c.816-10T>G	intron	N/A	ENSP00000499695.1	P55851
UCP2	ENST00000310473.11	TSL:1	c.816-10T>G	intron	N/A	ENSP00000312029.3
UCP2	ENST00000880151.1		c.849-10T>G	intron	N/A	ENSP00000550210.1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000252

AC:

AN:

238004

AF XY:

0.0000233

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1454808

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.000183

AC:

AN:

43784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39304

South Asian (SAS)

AF:

0.00

AC:

AN:

85236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108310

Other (OTH)

AF:

0.0000499

AC:

AN:

60136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000145

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41500

American (AMR)

AF:

0.00118

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.000227

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.83

dbscSNV1_RF

Benign

0.61

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over