3-12350797-A-G

Variant names:

• chr3-12350797-A-G
• rs12486170
• NM_138711.6:c.-8-28907A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138711.6(PPARG):​c.-8-28907A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,230 control chromosomes in the GnomAD database, including 5,374 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 (5374 hom., cov: 33)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 7 publications found

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]

PPARG Gene-Disease associations (from GenCC):

• PPARG-related familial partial lipodystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Genomics England PanelApp
• Berardinelli-Seip congenital lipodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138711.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	NM_138711.6	MANE Select	c.-8-28907A>G		intron	N/A	NP_619725.3
	PPARG	NM_001354666.3		c.-8-28907A>G		intron	N/A	NP_001341595.2
	PPARG	NM_001354667.3		c.-8-28907A>G		intron	N/A	NP_001341596.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.-8-28907A>G		intron	N/A	ENSP00000498313.1
	PPARG	ENST00000397010.7	TSL:1	c.-8-28907A>G		intron	N/A	ENSP00000380205.3
	PPARG	ENST00000397015.7	TSL:1	c.-8-28907A>G		intron	N/A	ENSP00000380210.3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37467 AN: 152112 Hom.: 5370 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.246 AC: 37477 AN: 152230 Hom.: 5374 Cov.: 33 AF XY: 0.247 AC XY: 18372 AN XY: 74410

African (AFR) AF: 0.105 AC: 4370 AN: 41564

American (AMR) AF: 0.266 AC: 4073 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1411 AN: 3472

East Asian (EAS) AF: 0.130 AC: 675 AN: 5176

South Asian (SAS) AF: 0.168 AC: 811 AN: 4822

European-Finnish (FIN) AF: 0.326 AC: 3446 AN: 10582

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21491 AN: 68008

Other (OTH) AF: 0.285 AC: 603 AN: 2114

Alfa AF: 0.251 Hom.: 695

Bravo AF: 0.238

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.58
DANN	Benign	0.58
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12486170; hg19: chr3-12392296;