Variant 5-149832947-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_133263.4(PPARGC1B):c.874C>A(p.Arg292Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0426 in 1,613,134 control chromosomes in the GnomAD database, including 2,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.076 ( 748 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1798 hom. )

Consequence

PPARGC1B
NM_133263.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

PPARGC1B (HGNC:30022): (PPARG coactivator 1 beta) The protein encoded by this gene stimulates the activity of several transcription factors and nuclear receptors, including estrogen receptor alpha, nuclear respiratory factor 1, and glucocorticoid receptor. The encoded protein may be involved in fat oxidation, non-oxidative glucose metabolism, and the regulation of energy expenditure. This protein is downregulated in prediabetic and type 2 diabetes mellitus patients. Certain allelic variations in this gene increase the risk of the development of obesity. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

PPARGC1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016933084).

BP6

Variant 5-149832947-C-A is Benign according to our data. Variant chr5-149832947-C-A is described in ClinVar as [Benign]. Clinvar id is 1288654.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4 linkuse as main transcript	c.874C>A	p.Arg292Ser	missense_variant	5/12	ENST00000309241.10	NP_573570.3	Q86YN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPARGC1B	ENST00000309241.10 linkuse as main transcript	c.874C>A	p.Arg292Ser	missense_variant	5/12	1	NM_133263.4	ENSP00000312649.5	Q86YN6-1
PPARGC1B	ENST00000394320.7 linkuse as main transcript	c.874C>A	p.Arg292Ser	missense_variant	5/11	1		ENSP00000377855.3	Q86YN6-3
PPARGC1B	ENST00000360453.8 linkuse as main transcript	c.757C>A	p.Arg253Ser	missense_variant	4/11	1		ENSP00000353638.4	Q86YN6-5
PPARGC1B	ENST00000403750.5 linkuse as main transcript	c.682C>A	p.Arg228Ser	missense_variant	4/11	2		ENSP00000384403.1	Q86YN6-6

Frequencies

GnomAD3 genomes

AF:

0.0758

AC:

11529

AN:

152090

Hom.:

746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0481

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.0726

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.0690

GnomAD3 exomes

AF:

0.0507

AC:

12600

AN:

248750

Hom.:

592

AF XY:

0.0494

AC XY:

6662

AN XY:

134986

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.0663

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0335

Gnomad OTH exome

AF:

0.0409

GnomAD4 exome

AF:

0.0391

AC:

57194

AN:

1460926

Hom.:

1798

Cov.:

AF XY:

0.0396

AC XY:

28799

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.173

Gnomad4 AMR exome

AF:

0.0261

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.0689

Gnomad4 FIN exome

AF:

0.0162

Gnomad4 NFE exome

AF:

0.0313

Gnomad4 OTH exome

AF:

0.0525

GnomAD4 genome

AF:

0.0758

AC:

11535

AN:

152208

Hom.:

748

Cov.:

AF XY:

0.0746

AC XY:

5554

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.0480

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.0722

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.0328

Gnomad4 OTH

AF:

0.0678

Alfa

AF:

0.0389

Hom.:

426

Bravo

AF:

0.0830

TwinsUK

AF:

0.0326

AC:

121

ALSPAC

AF:

0.0254

AC:

ESP6500AA

AF:

0.176

AC:

776

ESP6500EA

AF:

0.0340

AC:

292

ExAC

AF:

0.0543

AC:

6588

Asia WGS

AF:

0.0970

AC:

337

AN:

3478

EpiCase

AF:

0.0322

EpiControl

AF:

0.0342

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

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;.;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.64

T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.5

.;M;M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.14

T;T;D;T

Polyphen

1.0

D;D;D;.

Vest4

0.54

MPC

0.69

ClinPred

0.021

GERP RS

5.8

Varity_R

0.37

gMVP

0.31

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