NM_138711.6:c.529+357G>A

Variant names:

• chr3-12393109-G-A
• rs2938392
• NM_138711.6:c.529+357G>A

Variant summary

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

The NM_138711.6(PPARG):​c.529+357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 150,694 control chromosomes in the GnomAD database, including 13,630 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 0.40 (13630 hom., cov: 30)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 23 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Genomics England PanelApp
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.529+357G>A		intron_variant	Intron 5 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.529+357G>A		intron_variant	Intron 5 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 60926 AN: 150612 Hom.: 13630 Cov.: 30

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.404 AC: 60936 AN: 150694 Hom.: 13630 Cov.: 30 AF XY: 0.409 AC XY: 30020 AN XY: 73474

African (AFR) AF: 0.207 AC: 8461 AN: 40916

American (AMR) AF: 0.430 AC: 6525 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1283 AN: 3460

East Asian (EAS) AF: 0.572 AC: 2938 AN: 5136

South Asian (SAS) AF: 0.661 AC: 3164 AN: 4790

European-Finnish (FIN) AF: 0.474 AC: 4827 AN: 10186

Middle Eastern (MID) AF: 0.417 AC: 121 AN: 290

European-Non Finnish (NFE) AF: 0.480 AC: 32540 AN: 67750

Other (OTH) AF: 0.406 AC: 850 AN: 2096

Alfa AF: 0.443 Hom.: 19847

Bravo AF: 0.383

Asia WGS AF: 0.543 AC: 1882 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.62
PhyloP100		0.62
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: rs2938392; hg19: chr3-12434608;