rs4135263

chr3-12381767-T-C

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.390+276T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,064 control chromosomes in the GnomAD database, including 1,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1657 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.125

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=-0.83).
• BP6: Variant 3-12381767-T-C is Benign according to our data. Variant chr3-12381767-T-C is described in ClinVar as [Benign]. Clinvar id is 1261529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_138711.6	c.390+276T>C		intron_variant		ENST00000651735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000651735.1	c.390+276T>C		intron_variant			NM_138711.6	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21234 AN: 151948 Hom.: 1652 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.140 AC: 21261 AN: 152064 Hom.: 1657 Cov.: 32 AF XY: 0.140 AC XY: 10392 AN XY: 74322

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.145

Alfa AF: 0.152 Hom.: 1599

Bravo AF: 0.147

Asia WGS AF: 0.0620 AC: 215 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.7
Dann	Benign	0.50

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: rs4135263; hg19: chr3-12423266;