Genetic Variant PPARG:c.-8-29620G>A (chr3-12350084-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.-8-29620G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,116 control chromosomes in the GnomAD database, including 1,427 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 0.13 ( 1427 hom., cov: 32)

Consequence

PPARG
NM_138711.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

Publications

22 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.-8-29620G>A	intron	N/A	NP_619725.3	E9PFV2
PPARG	NM_001354666.3		c.-8-29620G>A	intron	N/A	NP_001341595.2	E9PFV2
PPARG	NM_001354667.3		c.-8-29620G>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.-8-29620G>A	intron	N/A	ENSP00000498313.1	E9PFV2
PPARG	ENST00000397010.7	TSL:1	c.-8-29620G>A	intron	N/A	ENSP00000380205.3	E9PFV2
PPARG	ENST00000397015.7	TSL:1	c.-8-29620G>A	intron	N/A	ENSP00000380210.3	E9PFV2

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20291

AN:

151998

Hom.:

1422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.0410

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.0985

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

GnomAD4 genome

AF:

0.134

AC:

20313

AN:

152116

Hom.:

1427

Cov.:

AF XY:

0.134

AC XY:

9936

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.172

AC:

7122

AN:

41492

American (AMR)

AF:

0.101

AC:

1545

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0683

AC:

237

AN:

3468

East Asian (EAS)

AF:

0.0409

AC:

212

AN:

5180

South Asian (SAS)

AF:

0.130

AC:

626

AN:

4818

European-Finnish (FIN)

AF:

0.156

AC:

1652

AN:

10582

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8665

AN:

67982

Other (OTH)

AF:

0.0974

AC:

206

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

910

1820

2730

3640

4550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.122

Hom.:

3233

Bravo

AF:

0.131

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.4

(source)

DANN

Benign

0.67

PhyloP100

0.082

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