3-12393109-G-A

Position:

• chr3-12393109-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.529+357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 150,694 control chromosomes in the GnomAD database, including 13,630 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 0.40 (13630 hom., cov: 30)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619

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 (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.529+357G>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.529+357G>A		intron_variant			NM_138711.6	ENSP00000498313	P1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 60926 AN: 150612 Hom.: 13630 Cov.: 30

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.404 AC: 60936 AN: 150694 Hom.: 13630 Cov.: 30 AF XY: 0.409 AC XY: 30020 AN XY: 73474

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.406

Alfa AF: 0.453 Hom.: 15656

Bravo AF: 0.383

Asia WGS AF: 0.543 AC: 1882 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.62

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: rs2938392; hg19: chr3-12434608;