3-12379590-C-T

Position:

• chr3-12379590-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138711.6(PPARG):​c.-8-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 909,472 control chromosomes in the GnomAD database, including 10,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1607 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8755 hom.)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.580

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-12379590-C-T is Benign according to our data. Variant chr3-12379590-C-T is described in ClinVar as [Benign]. Clinvar id is 1227468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-8-114C>T		intron_variant		ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.-8-114C>T		intron_variant			NM_138711.6	ENSP00000498313	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20982 AN: 152046 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.142 AC: 107649 AN: 757306 Hom.: 8755 AF XY: 0.141 AC XY: 55987 AN XY: 397548

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.000208

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.138 AC: 21011 AN: 152166 Hom.: 1607 Cov.: 32 AF XY: 0.138 AC XY: 10260 AN XY: 74388

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.143

Alfa AF: 0.141 Hom.: 208

Bravo AF: 0.145

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.97
CADD	Benign	0.85
DANN	Benign	0.37

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: rs28763893; hg19: chr3-12421089;