3-12408855-G-A

Variant names:

• chr3-12408855-G-A
• rs709149
• NM_138711.6:c.729+2774G>A

Variant summary

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

The NM_001354668.2(PPARG):​c.*2708G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,846 control chromosomes in the GnomAD database, including 7,866 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 0.31 (7866 hom., cov: 31)
• Consequence: PPARG NM_001354668.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354668.2. 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.729+2774G>A		intron	N/A	NP_619725.3
	PPARG	NM_001354668.2		c.*2708G>A		3_prime_UTR	Exon 5 of 5	NP_001341597.1
	PPARG	NM_001354670.2		c.*2708G>A		3_prime_UTR	Exon 6 of 6	NP_001341599.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.729+2774G>A		intron	N/A	ENSP00000498313.1
	PPARG	ENST00000287820.10	TSL:1	c.819+2774G>A		intron	N/A	ENSP00000287820.6
	PPARG	ENST00000397010.7	TSL:1	c.729+2774G>A		intron	N/A	ENSP00000380205.3

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46344 AN: 151734 Hom.: 7865 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.305 AC: 46353 AN: 151846 Hom.: 7866 Cov.: 31 AF XY: 0.305 AC XY: 22627 AN XY: 74172

African (AFR) AF: 0.161 AC: 6655 AN: 41456

American (AMR) AF: 0.277 AC: 4223 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1517 AN: 3464

East Asian (EAS) AF: 0.427 AC: 2201 AN: 5160

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4816

European-Finnish (FIN) AF: 0.387 AC: 4048 AN: 10468

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.373 AC: 25314 AN: 67908

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.352 Hom.: 30751

Bravo AF: 0.296

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-0.0010
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: rs709149; hg19: chr3-12450354;