chr3-12343043-G-A

Position:

• chr3-12343043-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.-9+30590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,024 control chromosomes in the GnomAD database, including 5,328 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 0.25 (5328 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-9+30590G>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.-9+30590G>A		intron_variant			NM_138711.6	ENSP00000498313	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37239 AN: 151906 Hom.: 5324 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.245 AC: 37248 AN: 152024 Hom.: 5328 Cov.: 31 AF XY: 0.246 AC XY: 18249 AN XY: 74320

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.283

Alfa AF: 0.169 Hom.: 487

Bravo AF: 0.237

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12490265; hg19: chr3-12384542;