chr3-12402345-A-G

Position:

• chr3-12402345-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138711.6(PPARG):​c.530-3537A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,054 control chromosomes in the GnomAD database, including 3,206 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 0.18 (3206 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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 (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.530-3537A>G		intron_variant		ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.530-3537A>G		intron_variant			NM_138711.6	ENSP00000498313	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26773 AN: 151936 Hom.: 3212 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.176 AC: 26762 AN: 152054 Hom.: 3206 Cov.: 32 AF XY: 0.180 AC XY: 13396 AN XY: 74328

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.172

Alfa AF: 0.197 Hom.: 4322

Bravo AF: 0.174

Asia WGS AF: 0.432 AC: 1502 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.69

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: rs4135275; hg19: chr3-12443844;