NM_138711.6:c.-8-18602A>G

Variant names:

• chr3-12361102-A-G
• rs1373640
• NM_138711.6:c.-8-18602A>G

Variant summary

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

The NM_138711.6(PPARG):​c.-8-18602A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,100 control chromosomes in the GnomAD database, including 43,370 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 0.75 (43370 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 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.-8-18602A>G		intron	N/A	NP_619725.3
	PPARG	NM_015869.5		c.82+9428A>G		intron	N/A	NP_056953.2
	PPARG	NM_001354666.3		c.-8-18602A>G		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.-8-18602A>G		intron	N/A	ENSP00000498313.1
	PPARG	ENST00000287820.10	TSL:1	c.82+9428A>G		intron	N/A	ENSP00000287820.6
	PPARG	ENST00000397010.7	TSL:1	c.-8-18602A>G		intron	N/A	ENSP00000380205.3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113581 AN: 151982 Hom.: 43317 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.747 AC: 113691 AN: 152100 Hom.: 43370 Cov.: 31 AF XY: 0.747 AC XY: 55554 AN XY: 74342

African (AFR) AF: 0.896 AC: 37221 AN: 41530

American (AMR) AF: 0.743 AC: 11344 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2142 AN: 3466

East Asian (EAS) AF: 0.867 AC: 4488 AN: 5174

South Asian (SAS) AF: 0.832 AC: 4012 AN: 4822

European-Finnish (FIN) AF: 0.644 AC: 6799 AN: 10560

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45552 AN: 67966

Other (OTH) AF: 0.715 AC: 1510 AN: 2112

Alfa AF: 0.684 Hom.: 55770

Bravo AF: 0.758

Asia WGS AF: 0.785 AC: 2726 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.55
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1373640; hg19: chr3-12402601;