Genetic Variant PPARG:c.-9+30590G>A (chr3-12343043-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_138711.6(PPARG):c.-9+30590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,024 control chromosomes in the GnomAD database, including 5,328 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 0.25 ( 5328 hom., cov: 31)

Consequence

PPARG
NM_138711.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.819

Publications

14 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138711.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARG	NM_138711.6	MANE Select	c.-9+30590G>A	intron	N/A	NP_619725.3	E9PFV2
PPARG	NM_001354666.3		c.-9+30590G>A	intron	N/A	NP_001341595.2	E9PFV2
PPARG	NM_001354667.3		c.-8-36661G>A	intron	N/A	NP_001341596.2	E9PFV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARG	ENST00000651735.1	MANE Select	c.-9+30590G>A	intron	N/A	ENSP00000498313.1	E9PFV2
PPARG	ENST00000397010.7	TSL:1	c.-9+30590G>A	intron	N/A	ENSP00000380205.3	E9PFV2
PPARG	ENST00000397015.7	TSL:1	c.-8-36661G>A	intron	N/A	ENSP00000380210.3	E9PFV2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37239

AN:

151906

Hom.:

5324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.281

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

GnomAD4 genome

AF:

0.245

AC:

37248

AN:

152024

Hom.:

5328

Cov.:

AF XY:

0.246

AC XY:

18249

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.105

AC:

4349

AN:

41474

American (AMR)

AF:

0.264

AC:

4027

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1401

AN:

3462

East Asian (EAS)

AF:

0.129

AC:

668

AN:

5174

South Asian (SAS)

AF:

0.163

AC:

783

AN:

4812

European-Finnish (FIN)

AF:

0.326

AC:

3443

AN:

10560

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21389

AN:

67952

Other (OTH)

AF:

0.283

AC:

597

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1396

2791

4187

5582

6978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.271

Hom.:

9173

Bravo

AF:

0.237

Asia WGS

AF:

0.218

AC:

758

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.39

(source)

DANN

Benign

0.64

PhyloP100

-0.82

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