3-12288912-G-A

Position:

• chr3-12288912-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000455517.6(PPARG):​c.-231G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 152,590 control chromosomes in the GnomAD database, including 16 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 0.011 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (0 hom.)
• Consequence: PPARG ENST00000455517.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1719/152320) while in subpopulation NFE AF= 0.0164 (1116/68030). AF 95% confidence interval is 0.0156. There are 16 homozygotes in gnomad4. There are 833 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1719 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_001354666.3	c.-83+1237G>A		intron_variant
PPARG	NM_001354669.2	c.-510+892G>A		intron_variant
PPARG	NM_001374261.3	c.-83+892G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000455517.6	c.-231G>A		5_prime_UTR_variant	1/2	1
PPARG	ENST00000397010.7	c.-83+1237G>A		intron_variant		1		P1
PPARG	ENST00000397015.7	c.-9+892G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1721 AN: 152202 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00741 AC: 2 AN: 270 Hom.: 0 Cov.: 0 AF XY: 0.00500 AC XY: 1 AN XY: 200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00962

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0113 AC: 1719 AN: 152320 Hom.: 16 Cov.: 32 AF XY: 0.0112 AC XY: 833 AN XY: 74484

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00993

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0152 Hom.: 15

Bravo AF: 0.00958

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17036170; hg19: chr3-12330411;