rs9817428

chr3-12298768-C-Achr3-12298768-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138711.6(PPARG):c.-83+9634C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,024 control chromosomes in the GnomAD database, including 7,450 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 0.31 (7450 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_138711.6	c.-83+9634C>A		intron_variant		ENST00000651735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000651735.1	c.-83+9634C>A		intron_variant			NM_138711.6	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46532 AN: 151904 Hom.: 7428 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.307 AC: 46596 AN: 152024 Hom.: 7450 Cov.: 32 AF XY: 0.310 AC XY: 23044 AN XY: 74284

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.274

Alfa AF: 0.263 Hom.: 5287

Bravo AF: 0.315

Asia WGS AF: 0.388 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.0
Dann	Benign	0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9817428; hg19: chr3-12340267;