dbSNP rs13073869: PPARG:c.-9+41G>A (chr3-12312494-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+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,076 control chromosomes in the GnomAD database, including 4,945 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 ( 4945 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PPARG
NM_138711.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600

Publications

13 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:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6 link	c.-9+41G>A		intron_variant	Intron 2 of 7	ENST00000651735.1	NP_619725.3	P37231E9PFV2D2KUA6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1 link	c.-9+41G>A		intron_variant	Intron 2 of 7		NM_138711.6	ENSP00000498313.1		E9PFV2

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38284

AN:

151958

Hom.:

4935

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.230

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.252

AC:

38322

AN:

152076

Hom.:

4945

Cov.:

AF XY:

0.252

AC XY:

18747

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.225

AC:

9331

AN:

41484

American (AMR)

AF:

0.289

AC:

4414

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

839

AN:

3470

East Asian (EAS)

AF:

0.326

AC:

1687

AN:

5172

South Asian (SAS)

AF:

0.227

AC:

1096

AN:

4824

European-Finnish (FIN)

AF:

0.280

AC:

2957

AN:

10552

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17326

AN:

67980

Other (OTH)

AF:

0.229

AC:

483

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1503

3006

4509

6012

7515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.223

Hom.:

1688

Bravo

AF:

0.256

Asia WGS

AF:

0.233

AC:

809

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.72

PhyloP100

0.0060

PromoterAI

0.012

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over