3-12433589-C-T

Variant names:

• chr3-12433589-C-T
• rs7626560
• NM_138711.6:c.1181-309C>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.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
• Publications: 16 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=-0.91).
• BP6: Variant 3-12433589-C-T is Benign according to our data. Variant chr3-12433589-C-T is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.1181-309C>T		intron_variant	Intron 7 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.1181-309C>T		intron_variant	Intron 7 of 7		NM_138711.6	ENSP00000498313.1

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

African (AFR) AF: 0.172 AC: 7075 AN: 41038

American (AMR) AF: 0.246 AC: 3727 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 706 AN: 3448

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5154

South Asian (SAS) AF: 0.130 AC: 618 AN: 4766

European-Finnish (FIN) AF: 0.134 AC: 1383 AN: 10288

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10609 AN: 67748

Other (OTH) AF: 0.182 AC: 382 AN: 2098

Alfa AF: 0.167 Hom.: 7159

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

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	-0.91
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.70
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: rs7626560; hg19: chr3-12475088;