3-12350084-G-A

Variant names:

• chr3-12350084-G-A
• rs2197423
• NM_138711.6:c.-8-29620G>A

Variant summary

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

The NM_138711.6(PPARG):​c.-8-29620G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,116 control chromosomes in the GnomAD database, including 1,427 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 0.13 (1427 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 22 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-8-29620G>A		intron_variant	Intron 2 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.-8-29620G>A		intron_variant	Intron 2 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20291 AN: 151998 Hom.: 1422 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.134 AC: 20313 AN: 152116 Hom.: 1427 Cov.: 32 AF XY: 0.134 AC XY: 9936 AN XY: 74360

African (AFR) AF: 0.172 AC: 7122 AN: 41492

American (AMR) AF: 0.101 AC: 1545 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5180

South Asian (SAS) AF: 0.130 AC: 626 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1652 AN: 10582

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8665 AN: 67982

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.122 Hom.: 3233

Bravo AF: 0.131

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.67
PhyloP100		0.082
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: rs2197423; hg19: chr3-12391583;