rs2920502

Variant names:

• chr3-12287696-G-C
• rs2920502
• ENST00000397010.7:c.-83+21G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-12287696-G-C
• chr3-12287696-G-T

Variant summary

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

The NM_001354666.3(PPARG):​c.-83+21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,278 control chromosomes in the GnomAD database, including 7,840 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 (7832 hom., cov: 29)
  • Exomes 𝑓: 0.40 (8 hom.)
• Consequence: PPARG NM_001354666.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 28 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: G2P, Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354666.3. 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_001354666.3		c.-83+21G>C		intron	N/A	NP_001341595.2	E9PFV2
	PPARG	NM_005037.7		c.-333G>C		upstream_gene	N/A	NP_005028.5
	PPARG	NM_138712.5		c.-407G>C		upstream_gene	N/A	NP_619726.3	E9PFV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000397010.7	TSL:1	c.-83+21G>C		intron	N/A	ENSP00000380205.3	E9PFV2
	PPARG	ENST00000942257.1		c.-412+21G>C		intron	N/A	ENSP00000612316.1
	PPARG	ENST00000397029.8	TSL:3	c.-9+21G>C		intron	N/A	ENSP00000380224.4	E7EUD1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43051 AN: 151086 Hom.: 7832 Cov.: 29

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.404 AC: 38 AN: 94 Hom.: 8 Cov.: 0 AF XY: 0.455 AC XY: 30 AN XY: 66

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.625 AC: 5 AN: 8

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.372 AC: 29 AN: 78

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.285 AC: 43051 AN: 151184 Hom.: 7832 Cov.: 29 AF XY: 0.294 AC XY: 21705 AN XY: 73840

African (AFR) AF: 0.112 AC: 4652 AN: 41430

American (AMR) AF: 0.366 AC: 5575 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 911 AN: 3456

East Asian (EAS) AF: 0.753 AC: 3812 AN: 5060

South Asian (SAS) AF: 0.580 AC: 2787 AN: 4802

European-Finnish (FIN) AF: 0.355 AC: 3703 AN: 10442

Middle Eastern (MID) AF: 0.333 AC: 94 AN: 282

European-Non Finnish (NFE) AF: 0.306 AC: 20616 AN: 67474

Other (OTH) AF: 0.302 AC: 628 AN: 2082

Alfa AF: 0.287 Hom.: 895

Bravo AF: 0.276

Asia WGS AF: 0.558 AC: 1894 AN: 3396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.37
PhyloP100		-0.064
PromoterAI		-0.015	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: rs2920502; hg19: chr3-12329195; COSMIC: COSV58892615; COSMIC: COSV58892615;