rs709151

Variant names:

• chr3-12413500-C-T
• rs709151
• NM_138711.6:c.730-3204C>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.730-3204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,016 control chromosomes in the GnomAD database, including 6,672 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 0.28 (6672 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 12 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.730-3204C>T		intron_variant	Intron 6 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.730-3204C>T		intron_variant	Intron 6 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42363 AN: 151898 Hom.: 6669 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.279 AC: 42373 AN: 152016 Hom.: 6672 Cov.: 32 AF XY: 0.279 AC XY: 20710 AN XY: 74306

African (AFR) AF: 0.139 AC: 5757 AN: 41460

American (AMR) AF: 0.256 AC: 3911 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2182 AN: 5174

South Asian (SAS) AF: 0.180 AC: 865 AN: 4812

European-Finnish (FIN) AF: 0.354 AC: 3734 AN: 10538

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23348 AN: 67988

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.320 Hom.: 10402

Bravo AF: 0.270

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.0
DANN	Benign	0.73
PhyloP100		0.11
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: rs709151; hg19: chr3-12454999;