rs10510412

Variant names:

• chr3-12305463-G-A
• rs10510412
• NM_138711.6:c.-82-6917G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-12305463-G-A
• chr3-12305463-G-C

Variant summary

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

The NM_138711.6(PPARG):​c.-82-6917G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,056 control chromosomes in the GnomAD database, including 4,844 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 0.25 (4844 hom., cov: 32)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARG	NM_138711.6	c.-82-6917G>A		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.-82-6917G>A		intron_variant	Intron 1 of 7		NM_138711.6	ENSP00000498313.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37883 AN: 151938 Hom.: 4835 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.249 AC: 37920 AN: 152056 Hom.: 4844 Cov.: 32 AF XY: 0.250 AC XY: 18551 AN XY: 74322

African (AFR) AF: 0.216 AC: 8968 AN: 41496

American (AMR) AF: 0.286 AC: 4362 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1689 AN: 5170

South Asian (SAS) AF: 0.227 AC: 1096 AN: 4828

European-Finnish (FIN) AF: 0.280 AC: 2956 AN: 10558

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

European-Non Finnish (NFE) AF: 0.255 AC: 17344 AN: 67952

Other (OTH) AF: 0.227 AC: 480 AN: 2112

Alfa AF: 0.157 Hom.: 348

Bravo AF: 0.252

Asia WGS AF: 0.233 AC: 808 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.45
DANN	Benign	0.55
PhyloP100		-0.097
PromoterAI		-0.018	Neutral
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: rs10510412; hg19: chr3-12346962;