rs3856806

chr3-12434058-C-T

• Frequency:
  • Genomes: 𝑓 0.11 (1149 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2568 hom.)
• Consequence: PPARG NM_138711 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.333

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 3:12434058-C>T is Benign according to our data. Variant chr3-12434058-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 8139. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.333 with no splicing effect.
• BA1: GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARG	NM_138711.6	c.1341C>T	p.His447=	synonymous_variant	8/8	ENST00000651735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARG	ENST00000651735.1	c.1341C>T	p.His447=	synonymous_variant	8/8		NM_138711.6	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17378 AN: 152060 Hom.: 1149 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0895

GnomAD3 exomes AF: 0.134 AC: 33702 AN: 251322 Hom.: 2568 AF XY: 0.136 AC XY: 18405 AN XY: 135826

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0734

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.128 AC: 187677 AN: 1461862 Hom.: 12668 AF XY: 0.129 AC XY: 93871 AN XY: 727234

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0740

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.122

Alfa AF: 0.120 Hom.: 2734

Bravo AF: 0.102

Asia WGS AF: 0.133 AC: 463 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.114

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK:

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2019	This variant is associated with the following publications: (PMID: 18992148, 17141766, 22575725, 21795447, 10851250, 21833536, 9467001) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 01, 2022	- -

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Dec 01, 2003

- -

Glioma susceptibility 1 Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 01, 2000

- -

Obesity Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Diabetes Mellitus, Noninsulin-Dependent, with Acanthosis Nigricans and Hypertension Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

PPARG-related familial partial lipodystrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

Cadd

Benign

5.6

Dann

Benign

0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3856806; hg19: chr3-12475557; COSMIC: COSV55140736;