rs2960422

Variant names:

• chr3-12293492-G-A
• rs2960422
• NM_138711.6:c.-83+4358G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-12293492-G-A
• chr3-12293492-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138711.6(PPARG):​c.-83+4358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,924 control chromosomes in the GnomAD database, including 26,020 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 0.58 (26020 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 14 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 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.-83+4358G>A		intron	N/A	NP_619725.3	E9PFV2
	PPARG	NM_001354666.3		c.-83+5817G>A		intron	N/A	NP_001341595.2	E9PFV2
	PPARG	NM_001354667.3		c.-9+4358G>A		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.-83+4358G>A		intron	N/A	ENSP00000498313.1	E9PFV2
	PPARG	ENST00000397010.7	TSL:1	c.-83+5817G>A		intron	N/A	ENSP00000380205.3	E9PFV2
	PPARG	ENST00000397015.7	TSL:1	c.-9+5472G>A		intron	N/A	ENSP00000380210.3	E9PFV2

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88611 AN: 151810 Hom.: 26000 Cov.: 31

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.584 AC: 88673 AN: 151924 Hom.: 26020 Cov.: 31 AF XY: 0.583 AC XY: 43304 AN XY: 74244

African (AFR) AF: 0.609 AC: 25242 AN: 41434

American (AMR) AF: 0.553 AC: 8442 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2367 AN: 5162

South Asian (SAS) AF: 0.645 AC: 3108 AN: 4822

European-Finnish (FIN) AF: 0.569 AC: 5986 AN: 10518

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39497 AN: 67942

Other (OTH) AF: 0.583 AC: 1228 AN: 2106

Alfa AF: 0.572 Hom.: 14354

Bravo AF: 0.581

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.78
PhyloP100		1.1
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: rs2960422; hg19: chr3-12334991;