chr3-12294148-A-T

Variant names:

• chr3-12294148-A-T
• rs6809631
• NM_138711.6:c.-83+5014A>T

Variant summary

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

The NM_138711.6(PPARG):​c.-83+5014A>T 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 152,030 control chromosomes in the GnomAD database, including 6,358 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 (6358 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 7 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-83+5014A>T		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.-83+5014A>T		intron_variant	Intron 1 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43271 AN: 151912 Hom.: 6350 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.285 AC: 43305 AN: 152030 Hom.: 6358 Cov.: 32 AF XY: 0.289 AC XY: 21487 AN XY: 74296

African (AFR) AF: 0.288 AC: 11947 AN: 41484

American (AMR) AF: 0.340 AC: 5206 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2496 AN: 5142

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4818

European-Finnish (FIN) AF: 0.309 AC: 3266 AN: 10554

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17507 AN: 67956

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.162 Hom.: 338

Bravo AF: 0.290

Asia WGS AF: 0.381 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.5
DANN	Benign	0.89
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: rs6809631; hg19: chr3-12335647;