rs11128603

Variant names:

• chr3-12344329-A-G
• rs11128603
• NM_138711.6:c.-9+31876A>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.-9+31876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,718 control chromosomes in the GnomAD database, including 1,417 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 0.13 (1417 hom., cov: 28)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• Publications: 23 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: G2P, Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• lipodystrophy

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	NM_138711.6	MANE Select	c.-9+31876A>G		intron	N/A	NP_619725.3	E9PFV2
	PPARG	NM_001354666.3		c.-9+31876A>G		intron	N/A	NP_001341595.2	E9PFV2
	PPARG	NM_001354667.3		c.-8-35375A>G		intron	N/A	NP_001341596.2	E9PFV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.-9+31876A>G		intron	N/A	ENSP00000498313.1	E9PFV2
	PPARG	ENST00000397010.7	TSL:1	c.-9+31876A>G		intron	N/A	ENSP00000380205.3	E9PFV2
	PPARG	ENST00000397015.7	TSL:1	c.-8-35375A>G		intron	N/A	ENSP00000380210.3	E9PFV2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20236 AN: 151600 Hom.: 1412 Cov.: 28

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0997

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

GnomAD4 genome AF: 0.134 AC: 20259 AN: 151718 Hom.: 1417 Cov.: 28 AF XY: 0.133 AC XY: 9896 AN XY: 74154

African (AFR) AF: 0.171 AC: 7068 AN: 41288

American (AMR) AF: 0.102 AC: 1558 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3468

East Asian (EAS) AF: 0.0395 AC: 204 AN: 5162

South Asian (SAS) AF: 0.131 AC: 630 AN: 4814

European-Finnish (FIN) AF: 0.155 AC: 1630 AN: 10518

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8667 AN: 67912

Other (OTH) AF: 0.0987 AC: 208 AN: 2108

Alfa AF: 0.130 Hom.: 183

Bravo AF: 0.131

Asia WGS AF: 0.0700 AC: 243 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.42
PhyloP100		-3.1
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: rs11128603; hg19: chr3-12385828;