chr3-12427090-C-G

Variant names:

• chr3-12427090-C-G
• rs13099828
• NM_138711.6:c.1181-6808C>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.1181-6808C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,158 control chromosomes in the GnomAD database, including 2,151 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 0.16 (2151 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.1181-6808C>G		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.1181-6808C>G		intron_variant	Intron 7 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23979 AN: 152040 Hom.: 2145 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.158 AC: 24004 AN: 152158 Hom.: 2151 Cov.: 32 AF XY: 0.158 AC XY: 11781 AN XY: 74392

African (AFR) AF: 0.116 AC: 4829 AN: 41530

American (AMR) AF: 0.242 AC: 3703 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3468

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5184

South Asian (SAS) AF: 0.136 AC: 655 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10572

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11599 AN: 67988

Other (OTH) AF: 0.177 AC: 373 AN: 2112

Alfa AF: 0.167 Hom.: 277

Bravo AF: 0.163

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.60
PhyloP100		0.29
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: rs13099828; hg19: chr3-12468589;