3-12353341-C-T

Variant names:

• chr3-12353341-C-T
• rs1899951
• NM_138711.6:c.-8-26363C>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.-8-26363C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,086 control chromosomes in the GnomAD database, including 8,090 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 0.25 (8090 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 40 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	NM_138711.6	MANE Select	c.-8-26363C>T		intron	N/A	NP_619725.3
	PPARG	NM_015869.5		c.82+1667C>T		intron	N/A	NP_056953.2
	PPARG	NM_001354666.3		c.-8-26363C>T		intron	N/A	NP_001341595.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.-8-26363C>T		intron	N/A	ENSP00000498313.1
	PPARG	ENST00000287820.10	TSL:1	c.82+1667C>T		intron	N/A	ENSP00000287820.6
	PPARG	ENST00000397010.7	TSL:1	c.-8-26363C>T		intron	N/A	ENSP00000380205.3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38437 AN: 151968 Hom.: 8060 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.253 AC: 38507 AN: 152086 Hom.: 8090 Cov.: 32 AF XY: 0.249 AC XY: 18513 AN XY: 74330

African (AFR) AF: 0.584 AC: 24192 AN: 41438

American (AMR) AF: 0.153 AC: 2344 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 250 AN: 3468

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5184

South Asian (SAS) AF: 0.131 AC: 633 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1662 AN: 10590

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8771 AN: 67996

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.166 Hom.: 4449

Bravo AF: 0.267

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1899951; hg19: chr3-12394840;