rs10510410

Variant names:

• chr3-12305239-A-C
• rs10510410
• NM_138711.6:c.-82-7141A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-12305239-A-C
• chr3-12305239-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138711.6(PPARG):​c.-82-7141A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,062 control chromosomes in the GnomAD database, including 5,984 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (5984 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-82-7141A>C		intron_variant	Intron 1 of 7	ENST00000651735.1	NP_619725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARG	ENST00000651735.1	c.-82-7141A>C		intron_variant	Intron 1 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42226 AN: 151944 Hom.: 5972 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.278 AC: 42267 AN: 152062 Hom.: 5984 Cov.: 32 AF XY: 0.278 AC XY: 20693 AN XY: 74326

African (AFR) AF: 0.311 AC: 12882 AN: 41484

American (AMR) AF: 0.305 AC: 4656 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5170

South Asian (SAS) AF: 0.228 AC: 1102 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3058 AN: 10550

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17322 AN: 67960

Other (OTH) AF: 0.249 AC: 527 AN: 2114

Alfa AF: 0.260 Hom.: 20582

Bravo AF: 0.284

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10510410; hg19: chr3-12346738;