rs2959273

Variant names:

• chr3-12401232-A-G
• rs2959273
• NM_138711.6:c.530-4650A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-12401232-A-G
• chr3-12401232-A-T

Variant summary

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

The NM_138711.6(PPARG):​c.530-4650A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,094 control chromosomes in the GnomAD database, including 35,793 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 0.68 (35793 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 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.530-4650A>G		intron	N/A	NP_619725.3
	PPARG	NM_015869.5		c.620-4650A>G		intron	N/A	NP_056953.2
	PPARG	NM_001354666.3		c.530-4650A>G		intron	N/A	NP_001341595.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.530-4650A>G		intron	N/A	ENSP00000498313.1
	PPARG	ENST00000287820.10	TSL:1	c.620-4650A>G		intron	N/A	ENSP00000287820.6
	PPARG	ENST00000397010.7	TSL:1	c.530-4650A>G		intron	N/A	ENSP00000380205.3

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103461 AN: 151976 Hom.: 35754 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.681 AC: 103557 AN: 152094 Hom.: 35793 Cov.: 32 AF XY: 0.681 AC XY: 50603 AN XY: 74326

African (AFR) AF: 0.795 AC: 32996 AN: 41494

American (AMR) AF: 0.704 AC: 10754 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3470

East Asian (EAS) AF: 0.576 AC: 2984 AN: 5184

South Asian (SAS) AF: 0.782 AC: 3767 AN: 4818

European-Finnish (FIN) AF: 0.616 AC: 6509 AN: 10570

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42643 AN: 67966

Other (OTH) AF: 0.647 AC: 1363 AN: 2108

Alfa AF: 0.662 Hom.: 14279

Bravo AF: 0.688

Asia WGS AF: 0.655 AC: 2279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2959273; hg19: chr3-12442731;