rs1175540

Variant names:

• chr3-12423744-C-A
• rs1175540
• NM_138711.6:c.1180+6590C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-12423744-C-A
• chr3-12423744-C-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.1180+6590C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,128 control chromosomes in the GnomAD database, including 16,205 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 0.43 (16205 hom., cov: 33)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 18 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.1180+6590C>A		intron_variant	Intron 7 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.1180+6590C>A		intron_variant	Intron 7 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 66004 AN: 152008 Hom.: 16172 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.434 AC: 66086 AN: 152128 Hom.: 16205 Cov.: 33 AF XY: 0.430 AC XY: 31958 AN XY: 74356

African (AFR) AF: 0.674 AC: 27963 AN: 41504

American (AMR) AF: 0.323 AC: 4933 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2175 AN: 5168

South Asian (SAS) AF: 0.181 AC: 874 AN: 4820

European-Finnish (FIN) AF: 0.356 AC: 3768 AN: 10580

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23516 AN: 67978

Other (OTH) AF: 0.426 AC: 899 AN: 2112

Alfa AF: 0.395 Hom.: 2169

Bravo AF: 0.449

Asia WGS AF: 0.368 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		0.31
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: rs1175540; hg19: chr3-12465243;