dbSNP rs10011540: UCP1:c.-113A>C (chr4-140568842-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0950

Publications

19 publications found

Variant links:

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]

UCP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
UCP1	NM_021833.5 link	c.-113A>C	5_prime_UTR_variant	Exon 1 of 6	ENST00000262999.4	NP_068605.1
UCP1	NM_001440546.1 link	c.-113A>C	5_prime_UTR_variant	Exon 1 of 6		NP_001427475.1
UCP1	XM_011532228.3 link	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 link	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.:

show subpopulations

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.:

AF XY:

0.0894

AC XY:

59377

AN XY:

664530

show subpopulations

African (AFR)

AF:

0.149

AC:

4570

AN:

30668

American (AMR)

AF:

0.120

AC:

4195

AN:

34868

Ashkenazi Jewish (ASJ)

AF:

0.0901

AC:

2218

AN:

24624

East Asian (EAS)

AF:

0.0737

AC:

2598

AN:

35260

South Asian (SAS)

AF:

0.156

AC:

12109

AN:

77800

European-Finnish (FIN)

AF:

0.0877

AC:

2927

AN:

33378

Middle Eastern (MID)

AF:

0.0792

AC:

393

AN:

4964

European-Non Finnish (NFE)

AF:

0.0802

AC:

84331

AN:

1051648

Other (OTH)

AF:

0.0881

AC:

4964

AN:

56346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5604

11208

16811

22415

28019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3312

6624

9936

13248

16560

<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:

0.103

AC:

15681

AN:

152224

Hom.:

892

Cov.:

AF XY:

0.104

AC XY:

7744

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.151

AC:

6272

AN:

41534

American (AMR)

AF:

0.0976

AC:

1492

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

324

AN:

3472

East Asian (EAS)

AF:

0.0701

AC:

362

AN:

5166

South Asian (SAS)

AF:

0.153

AC:

738

AN:

4826

European-Finnish (FIN)

AF:

0.0838

AC:

889

AN:

10612

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0783

AC:

5324

AN:

68004

Other (OTH)

AF:

0.0885

AC:

187

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

736

1471

2207

2942

3678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0846

Hom.:

773

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

(source)

DANN

Benign

0.31

PhyloP100

0.095

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over