rs13306745

Positions:

• chr3-12379557-G-T

Variant summary

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

The NM_138711.6(PPARG):​c.-8-147G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 717,230 control chromosomes in the GnomAD database, including 131 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 0.0044 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (111 hom.)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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]

PPARG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-8-147G>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.-8-147G>T		intron_variant			NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 671 AN: 152206 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00558 AC: 3155 AN: 564906 Hom.: 111 AF XY: 0.00519 AC XY: 1564 AN XY: 301470

Gnomad4 AFR exome AF: 0.000722

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0755

Gnomad4 SAS exome AF: 0.00159

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000833

Gnomad4 OTH exome AF: 0.00367

GnomAD4 genome AF: 0.00441 AC: 671 AN: 152324 Hom.: 20 Cov.: 32 AF XY: 0.00487 AC XY: 363 AN XY: 74490

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0741

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000963 Hom.: 1

Bravo AF: 0.00519

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13306745; hg19: chr3-12421056;