3-12302942-A-G

Variant names:

• chr3-12302942-A-G
• rs7620165
• NM_138711.6:c.-82-9438A>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.-82-9438A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,130 control chromosomes in the GnomAD database, including 5,241 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 0.24 (5241 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 13 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: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• lipodystrophy

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	NM_138711.6	MANE Select	c.-82-9438A>G		intron	N/A	NP_619725.3	E9PFV2
	PPARG	NM_001354666.3		c.-82-9438A>G		intron	N/A	NP_001341595.2	E9PFV2
	PPARG	NM_001354667.3		c.-9+13808A>G		intron	N/A	NP_001341596.2	E9PFV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.-82-9438A>G		intron	N/A	ENSP00000498313.1	E9PFV2
	PPARG	ENST00000397010.7	TSL:1	c.-82-9438A>G		intron	N/A	ENSP00000380205.3	E9PFV2
	PPARG	ENST00000397015.7	TSL:1	c.-9+14922A>G		intron	N/A	ENSP00000380210.3	E9PFV2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36578 AN: 152012 Hom.: 5239 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.240 AC: 36582 AN: 152130 Hom.: 5241 Cov.: 32 AF XY: 0.238 AC XY: 17729 AN XY: 74378

African (AFR) AF: 0.113 AC: 4692 AN: 41526

American (AMR) AF: 0.223 AC: 3403 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3468

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5186

South Asian (SAS) AF: 0.143 AC: 688 AN: 4828

European-Finnish (FIN) AF: 0.311 AC: 3287 AN: 10570

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21745 AN: 67960

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.293 Hom.: 17868

Bravo AF: 0.233

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.22
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7620165;

hg19: chr3-12344441;