chr3-12430372-C-T

Position:

• chr3-12430372-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.1181-3526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,996 control chromosomes in the GnomAD database, including 15,437 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 0.45 (15437 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.1181-3526C>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.1181-3526C>T		intron_variant			NM_138711.6	ENSP00000498313	P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68219 AN: 151878 Hom.: 15426 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.449 AC: 68267 AN: 151996 Hom.: 15437 Cov.: 32 AF XY: 0.444 AC XY: 32947 AN XY: 74270

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.459

Alfa AF: 0.472 Hom.: 16565

Bravo AF: 0.448

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.4
DANN	Benign	0.71

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: rs1152002; hg19: chr3-12471871;