rs2292101

Variant names:

• chr3-12393402-C-T
• rs2292101
• NM_138711.6:c.529+650C>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.529+650C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 152,040 control chromosomes in the GnomAD database, including 290 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 0.037 (290 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 22 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.529+650C>T		intron_variant	Intron 5 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.529+650C>T		intron_variant	Intron 5 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5668 AN: 151920 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0387

Gnomad OTH AF: 0.0437

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

GnomAD4 genome AF: 0.0373 AC: 5664 AN: 152040 Hom.: 290 Cov.: 32 AF XY: 0.0373 AC XY: 2774 AN XY: 74328

African (AFR) AF: 0.0120 AC: 499 AN: 41498

American (AMR) AF: 0.0195 AC: 297 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 131 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1485 AN: 5162

South Asian (SAS) AF: 0.0444 AC: 214 AN: 4820

European-Finnish (FIN) AF: 0.0284 AC: 300 AN: 10548

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0387 AC: 2629 AN: 67962

Other (OTH) AF: 0.0433 AC: 91 AN: 2104

Alfa AF: 0.0362 Hom.: 136

Bravo AF: 0.0364

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		-0.29
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: rs2292101; hg19: chr3-12434901;