3-12287696-G-T

Variant names:

• chr3-12287696-G-T
• rs2920502
• ENST00000397010.7:c.-83+21G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001354666.3(PPARG):​c.-83+21G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: PPARG NM_001354666.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 28 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354666.3. 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_001354666.3		c.-83+21G>T		intron	N/A	NP_001341595.2	E9PFV2
	PPARG	NM_005037.7		c.-333G>T		upstream_gene	N/A	NP_005028.5
	PPARG	NM_138712.5		c.-407G>T		upstream_gene	N/A	NP_619726.3	E9PFV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000397010.7	TSL:1	c.-83+21G>T		intron	N/A	ENSP00000380205.3	E9PFV2
	PPARG	ENST00000942257.1		c.-412+21G>T		intron	N/A	ENSP00000612316.1
	PPARG	ENST00000397029.8	TSL:3	c.-9+21G>T		intron	N/A	ENSP00000380224.4	E7EUD1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.62
PhyloP100		-0.064
PromoterAI		0.0078	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2920502; hg19: chr3-12329195;