3-12288284-C-T

Variant names:

• chr3-12288284-C-T
• rs17036160
• ENST00000397010.7:c.-83+609C>T

Variant summary

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

The ENST00000397010.7(PPARG):​c.-83+609C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 151,712 control chromosomes in the GnomAD database, including 752 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 0.088 (752 hom., cov: 31)
• Consequence: PPARG ENST00000397010.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• Publications: 30 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_001354666.3	c.-83+609C>T		intron_variant	Intron 1 of 7		NP_001341595.2
PPARG	NM_005037.7	c.-9+264C>T		intron_variant	Intron 1 of 6		NP_005028.5
PPARG	NM_138712.5	c.-83+264C>T		intron_variant	Intron 1 of 7		NP_619726.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000397010.7	c.-83+609C>T		intron_variant	Intron 1 of 7	1		ENSP00000380205.3
PPARG	ENST00000397015.7	c.-9+264C>T		intron_variant	Intron 1 of 6	1		ENSP00000380210.3
PPARG	ENST00000309576.11	c.-83+264C>T		intron_variant	Intron 1 of 7	2		ENSP00000312472.7

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13403 AN: 151600 Hom.: 749 Cov.: 31

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0628

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

GnomAD4 genome AF: 0.0883 AC: 13402 AN: 151712 Hom.: 752 Cov.: 31 AF XY: 0.0889 AC XY: 6591 AN XY: 74124

African (AFR) AF: 0.0206 AC: 852 AN: 41422

American (AMR) AF: 0.0851 AC: 1298 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3468

East Asian (EAS) AF: 0.0399 AC: 203 AN: 5092

South Asian (SAS) AF: 0.118 AC: 566 AN: 4806

European-Finnish (FIN) AF: 0.157 AC: 1652 AN: 10546

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8462 AN: 67806

Other (OTH) AF: 0.0621 AC: 131 AN: 2108

Alfa AF: 0.110 Hom.: 2215

Bravo AF: 0.0800

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.88
PhyloP100		2.5
PromoterAI		-0.033	Neutral
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: rs17036160; hg19: chr3-12329783;