3-12347064-A-C

Variant names:

• chr3-12347064-A-C
• rs10510418
• NM_138711.6:c.-8-32640A>C

Variant summary

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

The NM_138711.6(PPARG):​c.-8-32640A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,038 control chromosomes in the GnomAD database, including 5,442 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 (5442 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 16 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 (NFE) allele frequency at 95% confidence interval = 0.315 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.-8-32640A>C		intron	N/A	NP_619725.3
	PPARG	NM_001354666.3		c.-8-32640A>C		intron	N/A	NP_001341595.2
	PPARG	NM_001354667.3		c.-8-32640A>C		intron	N/A	NP_001341596.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.-8-32640A>C		intron	N/A	ENSP00000498313.1
	PPARG	ENST00000397010.7	TSL:1	c.-8-32640A>C		intron	N/A	ENSP00000380205.3
	PPARG	ENST00000397015.7	TSL:1	c.-8-32640A>C		intron	N/A	ENSP00000380210.3

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37677 AN: 151918 Hom.: 5437 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.248 AC: 37688 AN: 152038 Hom.: 5442 Cov.: 31 AF XY: 0.249 AC XY: 18482 AN XY: 74330

African (AFR) AF: 0.102 AC: 4228 AN: 41520

American (AMR) AF: 0.264 AC: 4029 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3468

East Asian (EAS) AF: 0.179 AC: 923 AN: 5170

South Asian (SAS) AF: 0.171 AC: 824 AN: 4814

European-Finnish (FIN) AF: 0.326 AC: 3443 AN: 10554

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21647 AN: 67928

Other (OTH) AF: 0.284 AC: 598 AN: 2106

Alfa AF: 0.303 Hom.: 9519

Bravo AF: 0.240

Asia WGS AF: 0.235 AC: 815 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		1.1
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: rs10510418; hg19: chr3-12388563;