dbSNP rs13076055: PPARG:c.-83+11363G>A (chr3-12300497-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 ENST00000651735.1(PPARG):c.-83+11363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,750 control chromosomes in the GnomAD database, including 6,333 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 0.28 ( 6333 hom., cov: 32)

Consequence

PPARG
ENST00000651735.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.980

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651735.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPARG	NM_138711.6	MANE Select	c.-83+11363G>A	intron	N/A	NP_619725.3
PPARG	NM_001354666.3		c.-82-11883G>A	intron	N/A	NP_001341595.2
PPARG	NM_001354667.3		c.-9+11363G>A	intron	N/A	NP_001341596.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPARG	ENST00000651735.1	MANE Select	c.-83+11363G>A	intron	N/A	ENSP00000498313.1
PPARG	ENST00000397010.7	TSL:1	c.-82-11883G>A	intron	N/A	ENSP00000380205.3
PPARG	ENST00000397015.7	TSL:1	c.-9+12477G>A	intron	N/A	ENSP00000380210.3

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43137

AN:

151646

Hom.:

6325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.259

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

GnomAD4 genome

AF:

0.284

AC:

43172

AN:

151750

Hom.:

6333

Cov.:

AF XY:

0.289

AC XY:

21413

AN XY:

74136

show subpopulations

African (AFR)

AF:

0.286

AC:

11830

AN:

41338

American (AMR)

AF:

0.341

AC:

5197

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

837

AN:

3466

East Asian (EAS)

AF:

0.485

AC:

2511

AN:

5172

South Asian (SAS)

AF:

0.273

AC:

1314

AN:

4814

European-Finnish (FIN)

AF:

0.311

AC:

3260

AN:

10470

Middle Eastern (MID)

AF:

0.234

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.257

AC:

17485

AN:

67926

Other (OTH)

AF:

0.260

AC:

548

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1569

3138

4708

6277

7846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.267

Hom.:

8927

Bravo

AF:

0.289

Asia WGS

AF:

0.380

AC:

1318

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.20

(source)

DANN

Benign

0.64

PhyloP100

-0.98

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