3-12385437-G-T

Variant names:

• chr3-12385437-G-T
• rs10510419
• NM_138711.6:c.390+3946G>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.390+3946G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,154 control chromosomes in the GnomAD database, including 1,631 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 0.14 (1631 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 25 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.390+3946G>T		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.390+3946G>T		intron_variant	Intron 4 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21135 AN: 152036 Hom.: 1626 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.139 AC: 21165 AN: 152154 Hom.: 1631 Cov.: 32 AF XY: 0.139 AC XY: 10342 AN XY: 74384

African (AFR) AF: 0.114 AC: 4728 AN: 41506

American (AMR) AF: 0.213 AC: 3260 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5190

South Asian (SAS) AF: 0.111 AC: 536 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9868 AN: 67998

Other (OTH) AF: 0.144 AC: 305 AN: 2112

Alfa AF: 0.143 Hom.: 3291

Bravo AF: 0.146

Asia WGS AF: 0.0580 AC: 202 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.68
PhyloP100		0.41
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: rs10510419; hg19: chr3-12426936;