rs3856806

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_138711.6(PPARG):c.1341C>T(p.His447His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,614,040 control chromosomes in the GnomAD database, including 13,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1153 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12668 hom. )

Consequence

PPARG
NM_138711.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.333

Publications

438 publications found

Variant links:

Genes affected

PPARG (HGNC:9236): (peroxisome proliferator activated receptor gamma) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

PPARG Gene-Disease associations (from GenCC):

PPARG-related familial partial lipodystrophy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Genomics England PanelApp
Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PPARG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 3-12434058-C-T is Benign according to our data. Variant chr3-12434058-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 8139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.333 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6 link	c.1341C>T	p.His447His	synonymous_variant	Exon 8 of 8	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1 link	c.1341C>T	p.His447His	synonymous_variant	Exon 8 of 8		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17378

AN:

152060

Hom.:

1149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0637

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0869

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.0895

GnomAD2 exomes

AF:

0.134

AC:

33702

AN:

251322

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.0629

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.0734

Gnomad EAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.128

AC:

187677

AN:

1461862

Hom.:

12668

Cov.:

AF XY:

0.129

AC XY:

93871

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0572

AC:

1914

AN:

33480

American (AMR)

AF:

0.107

AC:

4765

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0740

AC:

1935

AN:

26134

East Asian (EAS)

AF:

0.197

AC:

7821

AN:

39700

South Asian (SAS)

AF:

0.144

AC:

12408

AN:

86256

European-Finnish (FIN)

AF:

0.197

AC:

10507

AN:

53420

Middle Eastern (MID)

AF:

0.0820

AC:

473

AN:

5768

European-Non Finnish (NFE)

AF:

0.126

AC:

140514

AN:

1111988

Other (OTH)

AF:

0.122

AC:

7340

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10708

21416

32123

42831

53539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5098

10196

15294

20392

25490

<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:

0.114

AC:

17390

AN:

152178

Hom.:

1153

Cov.:

AF XY:

0.116

AC XY:

8636

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0638

AC:

2650

AN:

41532

American (AMR)

AF:

0.0869

AC:

1328

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

247

AN:

3468

East Asian (EAS)

AF:

0.229

AC:

1186

AN:

5170

South Asian (SAS)

AF:

0.151

AC:

729

AN:

4824

European-Finnish (FIN)

AF:

0.200

AC:

2122

AN:

10584

Middle Eastern (MID)

AF:

0.0479

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.131

AC:

8887

AN:

68000

Other (OTH)

AF:

0.0895

AC:

189

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

777

1554

2331

3108

3885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.121

Hom.:

5727

Bravo

AF:

0.102

Asia WGS

AF:

0.133

AC:

463

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.114

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 18992148, 17141766, 22575725, 21795447, 10851250, 21833536, 9467001) -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

INSULIN RESISTANCE, DIGENIC

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Glioma susceptibility 1

Benign:1

Jun 01, 2000

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Obesity

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PPARG POLYMORPHISM

Benign:1

Dec 01, 2003

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

PPARG-related familial partial lipodystrophy

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.1

(source)

DANN

Benign

0.53

PhyloP100

-0.33

Mutation Taster

=88/12

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