rs2067819

chr3-12317550-G-A

Variant summary

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

The NM_138711.6(PPARG):c.-9+5097G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,036 control chromosomes in the GnomAD database, including 3,798 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 0.22 (3798 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_138711.6	c.-9+5097G>A		intron_variant		ENST00000651735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000651735.1	c.-9+5097G>A		intron_variant			NM_138711.6	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33402 AN: 151918 Hom.: 3790 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0420

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.220 AC: 33445 AN: 152036 Hom.: 3798 Cov.: 32 AF XY: 0.219 AC XY: 16302 AN XY: 74296

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0419

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.185

Alfa AF: 0.221 Hom.: 3834

Bravo AF: 0.224

Asia WGS AF: 0.107 AC: 370 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2067819; hg19: chr3-12359049;