rs2938395

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-12387969-G-A
• chr3-12387969-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-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

African (AFR) AF: 0.795 AC: 32916 AN: 41426

American (AMR) AF: 0.704 AC: 10730 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1966 AN: 3468

East Asian (EAS) AF: 0.575 AC: 2960 AN: 5150

South Asian (SAS) AF: 0.779 AC: 3752 AN: 4818

European-Finnish (FIN) AF: 0.615 AC: 6476 AN: 10536

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42752 AN: 67948

Other (OTH) AF: 0.645 AC: 1364 AN: 2114

Alfa AF: 0.642 Hom.: 134947

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
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2938395; hg19: chr3-12429468;