rs73027210

Positions:

• chr3-12405769-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_138711.6(PPARG):​c.530-113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,037,274 control chromosomes in the GnomAD database, including 29 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 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (27 hom.)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.83).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00413 (630/152368) while in subpopulation AMR AF= 0.0112 (172/15302). AF 95% confidence interval is 0.00987. There are 2 homozygotes in gnomad4. There are 322 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 630 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.530-113G>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.530-113G>A		intron_variant			NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.00412 AC: 628 AN: 152250 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00466

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00433 AC: 3829 AN: 884906 Hom.: 27 AF XY: 0.00415 AC XY: 1908 AN XY: 459424

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.00531

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000225

Gnomad4 FIN exome AF: 0.00185

Gnomad4 NFE exome AF: 0.00472

Gnomad4 OTH exome AF: 0.00456

GnomAD4 genome AF: 0.00413 AC: 630 AN: 152368 Hom.: 2 Cov.: 32 AF XY: 0.00432 AC XY: 322 AN XY: 74496

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00466

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00470 Hom.: 1

Bravo AF: 0.00436

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.46
DANN	Benign	0.52

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: rs73027210; hg19: chr3-12447268;