rs7732671

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_133263.4(PPARGC1B):c.607G>C(p.Ala203Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 1,547,582 control chromosomes in the GnomAD database, including 6,416 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1015 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5401 hom. )

Consequence

PPARGC1B
NM_133263.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.132

Publications

53 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012690127).

BP6

Variant 5-149832680-G-C is Benign according to our data. Variant chr5-149832680-G-C is described in ClinVar as Benign. ClinVar VariationId is 2039.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4 link	c.607G>C	p.Ala203Pro	missense_variant	Exon 5 of 12	ENST00000309241.10	NP_573570.3	Q86YN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPARGC1B	ENST00000309241.10 link	c.607G>C	p.Ala203Pro	missense_variant	Exon 5 of 12	1	NM_133263.4	ENSP00000312649.5	Q86YN6-1
PPARGC1B	ENST00000394320.7 link	c.607G>C	p.Ala203Pro	missense_variant	Exon 5 of 11	1		ENSP00000377855.3	Q86YN6-3
PPARGC1B	ENST00000360453.8 link	c.490G>C	p.Ala164Pro	missense_variant	Exon 4 of 11	1		ENSP00000353638.4	Q86YN6-5
PPARGC1B	ENST00000403750.5 link	c.415G>C	p.Ala139Pro	missense_variant	Exon 4 of 11	2		ENSP00000384403.1	Q86YN6-6

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16510

AN:

152060

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0597

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0804

Gnomad OTH

AF:

0.117

GnomAD2 exomes

AF:

0.0939

AC:

19531

AN:

207962

AF XY:

0.0905

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.0640

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.0836

Gnomad OTH exome

AF:

0.0859

GnomAD4 exome

AF:

0.0848

AC:

118292

AN:

1395404

Hom.:

5401

Cov.:

AF XY:

0.0840

AC XY:

57570

AN XY:

685398

show subpopulations

African (AFR)

AF:

0.162

AC:

5084

AN:

31430

American (AMR)

AF:

0.153

AC:

5524

AN:

36212

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3325

AN:

22668

East Asian (EAS)

AF:

0.0580

AC:

2252

AN:

38820

South Asian (SAS)

AF:

0.0651

AC:

4908

AN:

75436

European-Finnish (FIN)

AF:

0.0498

AC:

2571

AN:

51656

Middle Eastern (MID)

AF:

0.105

AC:

577

AN:

5470

European-Non Finnish (NFE)

AF:

0.0825

AC:

88736

AN:

1076220

Other (OTH)

AF:

0.0924

AC:

5315

AN:

57492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

5401

10802

16202

21603

27004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3522

7044

10566

14088

17610

<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:

0.109

AC:

16545

AN:

152178

Hom.:

1015

Cov.:

AF XY:

0.109

AC XY:

8134

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.161

AC:

6673

AN:

41506

American (AMR)

AF:

0.161

AC:

2463

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

488

AN:

3470

East Asian (EAS)

AF:

0.0598

AC:

309

AN:

5166

South Asian (SAS)

AF:

0.0613

AC:

295

AN:

4812

European-Finnish (FIN)

AF:

0.0462

AC:

490

AN:

10612

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0804

AC:

5470

AN:

68002

Other (OTH)

AF:

0.116

AC:

245

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

738

1476

2213

2951

3689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.0910

Hom.:

476

Bravo

AF:

0.119

TwinsUK

AF:

0.0774

AC:

287

ALSPAC

AF:

0.0825

AC:

318

ESP6500AA

AF:

0.161

AC:

708

ESP6500EA

AF:

0.0841

AC:

723

ExAC

AF:

0.0916

AC:

11106

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 15863669, 19653005, 16704985) -

PPARGC1B polymorphism

Benign:1

May 01, 2005

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.4

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.083

.;.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.51

T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

.;L;L;.

PhyloP100

0.13

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.030

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.0030

B;B;B;.

Vest4

0.10

MPC

0.21

ClinPred

0.0026

GERP RS

-4.3

PromoterAI

0.0014

Neutral

(source)

Varity_R

0.050

gMVP

0.073

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over