rs2960422

chr3-12293492-G-Achr3-12293492-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138711.6(PPARG):c.-83+4358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,924 control chromosomes in the GnomAD database, including 26,020 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 0.58 (26020 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_138711.6	c.-83+4358G>A		intron_variant		ENST00000651735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000651735.1	c.-83+4358G>A		intron_variant			NM_138711.6	P1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88611 AN: 151810 Hom.: 26000 Cov.: 31

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.584 AC: 88673 AN: 151924 Hom.: 26020 Cov.: 31 AF XY: 0.583 AC XY: 43304 AN XY: 74244

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.583

Alfa AF: 0.577 Hom.: 6763

Bravo AF: 0.581

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	17
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2960422; hg19: chr3-12334991;