Genetic Variant NM_138711.6:c.-9+17130G>C (chr3-12329583-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138711.6(PPARG):c.-9+17130G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,920 control chromosomes in the GnomAD database, including 5,754 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 0.27 ( 5754 hom., cov: 32)

Consequence

PPARG
NM_138711.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

10 publications found

Variant links:

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

PPARG links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138711.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPARG	NM_138711.6	MANE Select	c.-9+17130G>C	intron	N/A	NP_619725.3
PPARG	NM_001354666.3		c.-9+17130G>C	intron	N/A	NP_001341595.2
PPARG	NM_001354667.3		c.-9+40449G>C	intron	N/A	NP_001341596.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPARG	ENST00000651735.1	MANE Select	c.-9+17130G>C	intron	N/A	ENSP00000498313.1
PPARG	ENST00000397010.7	TSL:1	c.-9+17130G>C	intron	N/A	ENSP00000380205.3
PPARG	ENST00000397015.7	TSL:1	c.-9+41563G>C	intron	N/A	ENSP00000380210.3

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41410

AN:

151802

Hom.:

5737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.243

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

GnomAD4 genome

AF:

0.273

AC:

41467

AN:

151920

Hom.:

5754

Cov.:

AF XY:

0.273

AC XY:

20235

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.298

AC:

12343

AN:

41418

American (AMR)

AF:

0.297

AC:

4523

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

838

AN:

3460

East Asian (EAS)

AF:

0.327

AC:

1694

AN:

5180

South Asian (SAS)

AF:

0.227

AC:

1091

AN:

4812

European-Finnish (FIN)

AF:

0.280

AC:

2954

AN:

10546

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.255

AC:

17325

AN:

67934

Other (OTH)

AF:

0.242

AC:

511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1544

3087

4631

6174

7718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.269

Hom.:

819

Bravo

AF:

0.280

Asia WGS

AF:

0.238

AC:

825

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.49

(source)

DANN

Benign

0.46

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over