NM_138711.6:c.530-228G>T

Variant names:

• chr3-12405654-G-T
• rs1151999
• NM_138711.6:c.530-228G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138711.6(PPARG):​c.530-228G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,086 control chromosomes in the GnomAD database, including 28,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (28626 hom., cov: 33)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89
• Publications: 20 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-12405654-G-T is Benign according to our data. Variant chr3-12405654-G-T is described in ClinVar as Benign. ClinVar VariationId is 1233710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.530-228G>T		intron_variant	Intron 5 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.530-228G>T		intron_variant	Intron 5 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90842 AN: 151968 Hom.: 28574 Cov.: 33

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.598 AC: 90952 AN: 152086 Hom.: 28626 Cov.: 33 AF XY: 0.594 AC XY: 44142 AN XY: 74324

African (AFR) AF: 0.801 AC: 33236 AN: 41492

American (AMR) AF: 0.569 AC: 8692 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2152 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2202 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4816

European-Finnish (FIN) AF: 0.538 AC: 5672 AN: 10550

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35277 AN: 67988

Other (OTH) AF: 0.599 AC: 1264 AN: 2110

Alfa AF: 0.554 Hom.: 69237

Bravo AF: 0.617

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		1.9
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: rs1151999; hg19: chr3-12447153;