rs4684847

Positions:

• chr3-12344838-C-T

Variant summary

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

The NM_138711.6(PPARG):​c.-9+32385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,140 control chromosomes in the GnomAD database, including 766 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 0.089 (766 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-9+32385C>T		intron_variant		ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.-9+32385C>T		intron_variant			NM_138711.6	ENSP00000498313	P1

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13578 AN: 152022 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.0578

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0633

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0892 AC: 13575 AN: 152140 Hom.: 766 Cov.: 32 AF XY: 0.0898 AC XY: 6674 AN XY: 74354

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.0578

Gnomad4 EAS AF: 0.0406

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.109 Hom.: 965

Bravo AF: 0.0802

Asia WGS AF: 0.0570 AC: 198 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.7
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4684847; hg19: chr3-12386337;