rs13061415

Variant names:

• chr3-12308425-T-C
• rs13061415
• NM_138711.6:c.-82-3955T>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.-82-3955T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 148,904 control chromosomes in the GnomAD database, including 5,927 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 0.28 (5927 hom., cov: 29)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-82-3955T>C		intron_variant	Intron 1 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.-82-3955T>C		intron_variant	Intron 1 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 41535 AN: 148814 Hom.: 5914 Cov.: 29

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.279 AC: 41576 AN: 148904 Hom.: 5927 Cov.: 29 AF XY: 0.280 AC XY: 20240 AN XY: 72396

African (AFR) AF: 0.318 AC: 12830 AN: 40304

American (AMR) AF: 0.305 AC: 4544 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 814 AN: 3438

East Asian (EAS) AF: 0.331 AC: 1672 AN: 5044

South Asian (SAS) AF: 0.231 AC: 1079 AN: 4680

European-Finnish (FIN) AF: 0.281 AC: 2744 AN: 9748

Middle Eastern (MID) AF: 0.232 AC: 66 AN: 284

European-Non Finnish (NFE) AF: 0.255 AC: 17184 AN: 67518

Other (OTH) AF: 0.253 AC: 522 AN: 2062

Alfa AF: 0.269 Hom.: 8945

Bravo AF: 0.285

Asia WGS AF: 0.235 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.59
PhyloP100		-0.42
PromoterAI		-0.022	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: rs13061415; hg19: chr3-12349924;