Variant 4-140562322-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021833.5(UCP1):c.680C>T(p.Thr227Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,128 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 15 hom. )

Consequence

UCP1
NM_021833.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.96

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028290689).

BP6

Variant 4-140562322-G-A is Benign according to our data. Variant chr4-140562322-G-A is described in ClinVar as [Benign]. Clinvar id is 773711.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UCP1	NM_021833.5 linkuse as main transcript	c.680C>T	p.Thr227Ile	missense_variant	5/6	ENST00000262999.4
UCP1	XM_005263206.4 linkuse as main transcript	c.677C>T	p.Thr226Ile	missense_variant	5/6
UCP1	XM_011532228.3 linkuse as main transcript	c.680C>T	p.Thr227Ile	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP1	ENST00000262999.4 linkuse as main transcript	c.680C>T	p.Thr227Ile	missense_variant	5/6	1	NM_021833.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

111

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00198

AC:

499

AN:

251440

Hom.:

AF XY:

0.00280

AC XY:

381

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000571

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00131

AC:

1922

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1272

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000538

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152266

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000518

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00209

AC:

254

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Pathogenic

0.21

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

MetaRNN

Benign

0.028

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.020

Polyphen

0.48

Vest4

0.91

MVP

0.85

MPC

0.55

ClinPred

0.060

GERP RS

4.9

Varity_R

0.85

gMVP

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over