3-12433589-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138711.6(PPARG):c.1181-309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 150,898 control chromosomes in the GnomAD database, including 2,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2254 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.700

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-12433589-C-T is Benign according to our data. Variant chr3-12433589-C-T is described in ClinVar as [Benign]. Clinvar id is 1238427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_138711.6	c.1181-309C>T		intron_variant		ENST00000651735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000651735.1	c.1181-309C>T		intron_variant			NM_138711.6	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24773 AN: 150784 Hom.: 2250 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.164 AC: 24801 AN: 150898 Hom.: 2254 Cov.: 31 AF XY: 0.164 AC XY: 12084 AN XY: 73662

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.182

Alfa AF: 0.165 Hom.: 4570

Bravo AF: 0.176

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.60

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: rs7626560; hg19: chr3-12475088;