chr3-12387969-G-A

Variant names:

• chr3-12387969-G-A
• rs2938395
• NM_138711.6:c.391-4645G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138711.6(PPARG):​c.391-4645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 151,910 control chromosomes in the GnomAD database, including 35,776 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 0.68 (35776 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.391-4645G>A		intron_variant	Intron 4 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.391-4645G>A		intron_variant	Intron 4 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103422 AN: 151792 Hom.: 35740 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.681 AC: 103516 AN: 151910 Hom.: 35776 Cov.: 31 AF XY: 0.681 AC XY: 50554 AN XY: 74208

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.645

Alfa AF: 0.634 Hom.: 61864

Bravo AF: 0.688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2938395; hg19: chr3-12429468;