NM_138711.6:c.530-4548T>G

Variant names:

• chr3-12401334-T-G
• rs2959272
• NM_138711.6:c.530-4548T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138711.6(PPARG):​c.530-4548T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,956 control chromosomes in the GnomAD database, including 20,793 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 0.52 (20793 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 20 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.65 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	NM_138711.6	MANE Select	c.530-4548T>G		intron	N/A	NP_619725.3	E9PFV2
	PPARG	NM_015869.5		c.620-4548T>G		intron	N/A	NP_056953.2
	PPARG	NM_001354666.3		c.530-4548T>G		intron	N/A	NP_001341595.2	E9PFV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.530-4548T>G		intron	N/A	ENSP00000498313.1	E9PFV2
	PPARG	ENST00000287820.10	TSL:1	c.620-4548T>G		intron	N/A	ENSP00000287820.6	P37231-1
	PPARG	ENST00000397010.7	TSL:1	c.530-4548T>G		intron	N/A	ENSP00000380205.3	E9PFV2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78703 AN: 151838 Hom.: 20780 Cov.: 31

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.518 AC: 78750 AN: 151956 Hom.: 20793 Cov.: 31 AF XY: 0.519 AC XY: 38499 AN XY: 74242

African (AFR) AF: 0.599 AC: 24822 AN: 41458

American (AMR) AF: 0.481 AC: 7346 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2960 AN: 5156

South Asian (SAS) AF: 0.669 AC: 3212 AN: 4802

European-Finnish (FIN) AF: 0.466 AC: 4918 AN: 10550

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32780 AN: 67930

Other (OTH) AF: 0.482 AC: 1019 AN: 2112

Alfa AF: 0.486 Hom.: 30373

Bravo AF: 0.514

Asia WGS AF: 0.569 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.74
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2959272; hg19: chr3-12442833;