chr3-12312494-G-A

Position:

• chr3-12312494-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+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,076 control chromosomes in the GnomAD database, including 4,945 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 0.25 (4945 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-9+41G>A		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+41G>A		intron_variant			NM_138711.6	ENSP00000498313	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38284 AN: 151958 Hom.: 4935 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.252 AC: 38322 AN: 152076 Hom.: 4945 Cov.: 32 AF XY: 0.252 AC XY: 18747 AN XY: 74330

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.229

Alfa AF: 0.162 Hom.: 441

Bravo AF: 0.256

Asia WGS AF: 0.233 AC: 809 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13073869; hg19: chr3-12353993;