Genetic Variant PPARG:c.-83+609C>T (chr3-12288284-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005037.7(PPARG):c.-9+264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 151,712 control chromosomes in the GnomAD database, including 752 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 0.088 ( 752 hom., cov: 31)

Consequence

PPARG
NM_005037.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51

Publications

30 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: G2P, Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
lipodystrophy
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PPARG 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 (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005037.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARG	NM_001354666.3	c.-83+609C>T	intron	N/A	NP_001341595.2	E9PFV2
PPARG	NM_005037.7	c.-9+264C>T	intron	N/A	NP_005028.5
PPARG	NM_138712.5	c.-83+264C>T	intron	N/A	NP_619726.3	E9PFV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARG	ENST00000397010.7	TSL:1	c.-83+609C>T	intron	N/A	ENSP00000380205.3	E9PFV2
PPARG	ENST00000397015.7	TSL:1	c.-9+264C>T	intron	N/A	ENSP00000380210.3	E9PFV2
PPARG	ENST00000309576.11	TSL:2	c.-83+264C>T	intron	N/A	ENSP00000312472.7	E9PFV2

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13403

AN:

151600

Hom.:

749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0207

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0852

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.0397

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.0628

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0883

AC:

13402

AN:

151712

Hom.:

752

Cov.:

AF XY:

0.0889

AC XY:

6591

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.0206

AC:

852

AN:

41422

American (AMR)

AF:

0.0851

AC:

1298

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3468

East Asian (EAS)

AF:

0.0399

AC:

203

AN:

5092

South Asian (SAS)

AF:

0.118

AC:

566

AN:

4806

European-Finnish (FIN)

AF:

0.157

AC:

1652

AN:

10546

Middle Eastern (MID)

AF:

0.0548

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.125

AC:

8462

AN:

67806

Other (OTH)

AF:

0.0621

AC:

131

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

588

1175

1763

2350

2938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.110

Hom.:

2215

Bravo

AF:

0.0800

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.6

(source)

DANN

Benign

0.88

PhyloP100

2.5

PromoterAI

-0.033

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over