Genetic Variant PPARG:c.529+357G>A (chr3-12393109-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.529+357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 150,694 control chromosomes in the GnomAD database, including 13,630 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 0.40 ( 13630 hom., cov: 30)

Consequence

PPARG
NM_138711.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.619

Publications

23 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 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.529+357G>A	intron	N/A	NP_619725.3	E9PFV2
PPARG	NM_015869.5		c.619+357G>A	intron	N/A	NP_056953.2
PPARG	NM_001354666.3		c.529+357G>A	intron	N/A	NP_001341595.2	E9PFV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARG	ENST00000651735.1	MANE Select	c.529+357G>A	intron	N/A	ENSP00000498313.1	E9PFV2
PPARG	ENST00000287820.10	TSL:1	c.619+357G>A	intron	N/A	ENSP00000287820.6	P37231-1
PPARG	ENST00000397010.7	TSL:1	c.529+357G>A	intron	N/A	ENSP00000380205.3	E9PFV2

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

60926

AN:

150612

Hom.:

13630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.423

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.406

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

GnomAD4 genome

AF:

0.404

AC:

60936

AN:

150694

Hom.:

13630

Cov.:

AF XY:

0.409

AC XY:

30020

AN XY:

73474

show subpopulations

African (AFR)

AF:

0.207

AC:

8461

AN:

40916

American (AMR)

AF:

0.430

AC:

6525

AN:

15162

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1283

AN:

3460

East Asian (EAS)

AF:

0.572

AC:

2938

AN:

5136

South Asian (SAS)

AF:

0.661

AC:

3164

AN:

4790

European-Finnish (FIN)

AF:

0.474

AC:

4827

AN:

10186

Middle Eastern (MID)

AF:

0.417

AC:

121

AN:

290

European-Non Finnish (NFE)

AF:

0.480

AC:

32540

AN:

67750

Other (OTH)

AF:

0.406

AC:

850

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1696

3392

5087

6783

8479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.443

Hom.:

19847

Bravo

AF:

0.383

Asia WGS

AF:

0.543

AC:

1882

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.7

(source)

DANN

Benign

0.62

PhyloP100

0.62

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over