rs2920502

chr3-12287696-G-Cchr3-12287696-G-T

Variant summary

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

The ENST00000397010.7(PPARG):c.-83+21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,278 control chromosomes in the GnomAD database, including 7,840 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 0.28 (7832 hom., cov: 29)
  • Exomes 𝑓: 0.40 (8 hom.)
• Consequence: PPARG ENST00000397010.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_001354666.3	c.-83+21G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000397010.7	c.-83+21G>C		intron_variant		1		P1
PPARG	ENST00000397029.8	c.-9+21G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43051 AN: 151086 Hom.: 7832 Cov.: 29

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.404 AC: 38 AN: 94 Hom.: 8 Cov.: 0 AF XY: 0.455 AC XY: 30 AN XY: 66

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.285 AC: 43051 AN: 151184 Hom.: 7832 Cov.: 29 AF XY: 0.294 AC XY: 21705 AN XY: 73840

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.302

Alfa AF: 0.287 Hom.: 895

Bravo AF: 0.276

Asia WGS AF: 0.558 AC: 1894 AN: 3396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.6
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2920502; hg19: chr3-12329195; COSMIC: COSV58892615; COSMIC: COSV58892615;