3-12303137-A-G

Variant names:

• chr3-12303137-A-G
• rs11128597
• NM_138711.6:c.-82-9243A>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.-82-9243A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,974 control chromosomes in the GnomAD database, including 6,432 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 0.29 (6432 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-82-9243A>G		intron_variant	Intron 1 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.-82-9243A>G		intron_variant	Intron 1 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43470 AN: 151858 Hom.: 6421 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.286 AC: 43508 AN: 151974 Hom.: 6432 Cov.: 31 AF XY: 0.290 AC XY: 21571 AN XY: 74268

African (AFR) AF: 0.288 AC: 11926 AN: 41446

American (AMR) AF: 0.345 AC: 5279 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 855 AN: 3468

East Asian (EAS) AF: 0.488 AC: 2519 AN: 5160

South Asian (SAS) AF: 0.274 AC: 1319 AN: 4810

European-Finnish (FIN) AF: 0.311 AC: 3276 AN: 10542

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17591 AN: 67954

Other (OTH) AF: 0.262 AC: 552 AN: 2108

Alfa AF: 0.268 Hom.: 11450

Bravo AF: 0.292

Asia WGS AF: 0.382 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.68
PhyloP100		1.1
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: rs11128597; hg19: chr3-12344636;