dbSNP rs2028760: PPARG:c.-9+18930G>A (chr3-12331383-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+18930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,092 control chromosomes in the GnomAD database, including 4,936 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 ( 4936 hom., cov: 32)

Consequence

PPARG
NM_138711.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.383

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: 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 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+18930G>A	intron	N/A	NP_619725.3	E9PFV2
PPARG	NM_001354666.3		c.-9+18930G>A	intron	N/A	NP_001341595.2	E9PFV2
PPARG	NM_001354667.3		c.-9+42249G>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+18930G>A	intron	N/A	ENSP00000498313.1	E9PFV2
PPARG	ENST00000397010.7	TSL:1	c.-9+18930G>A	intron	N/A	ENSP00000380205.3	E9PFV2
PPARG	ENST00000397015.7	TSL:1	c.-9+43363G>A	intron	N/A	ENSP00000380210.3	E9PFV2

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38208

AN:

151974

Hom.:

4927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.229

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

GnomAD4 genome

AF:

0.251

AC:

38245

AN:

152092

Hom.:

4936

Cov.:

AF XY:

0.251

AC XY:

18686

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.225

AC:

9322

AN:

41508

American (AMR)

AF:

0.287

AC:

4385

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

836

AN:

3470

East Asian (EAS)

AF:

0.326

AC:

1688

AN:

5174

South Asian (SAS)

AF:

0.227

AC:

1093

AN:

4822

European-Finnish (FIN)

AF:

0.279

AC:

2949

AN:

10566

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17300

AN:

67980

Other (OTH)

AF:

0.228

AC:

482

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1435

2870

4304

5739

7174

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:

0.252

Hom.:

8343

Bravo

AF:

0.256

Asia WGS

AF:

0.233

AC:

808

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.77

(source)

DANN

Benign

0.44

PhyloP100

-0.38

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