Genetic Variant ENST00000397010.7:c.-83+21G>C (chr3-12287696-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 ENST00000397010.7(PPARG):c.-83+21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,278 control chromosomes in the GnomAD database, including 7,840 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 ( 7832 hom., cov: 29)

Exomes 𝑓: 0.40 ( 8 hom. )

Consequence

PPARG
ENST00000397010.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

29 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
lipodystrophy
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PPARG links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000397010.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397010.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARG	NM_001354666.3	c.-83+21G>C	intron	N/A	NP_001341595.2	E9PFV2
PPARG	NM_005037.7	c.-333G>C	upstream_gene	N/A	NP_005028.5
PPARG	NM_138712.5	c.-407G>C	upstream_gene	N/A	NP_619726.3	E9PFV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARG	ENST00000397010.7	TSL:1	c.-83+21G>C	intron	N/A	ENSP00000380205.3	E9PFV2
PPARG	ENST00000942257.1		c.-412+21G>C	intron	N/A	ENSP00000612316.1
PPARG	ENST00000397029.8	TSL:3	c.-9+21G>C	intron	N/A	ENSP00000380224.4	E7EUD1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43051

AN:

151086

Hom.:

7832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.346

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.300

GnomAD4 exome

AF:

0.404

AC:

AN:

Hom.:

Cov.:

AF XY:

0.455

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.625

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.372

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.285

AC:

43051

AN:

151184

Hom.:

7832

Cov.:

AF XY:

0.294

AC XY:

21705

AN XY:

73840

show subpopulations

African (AFR)

AF:

0.112

AC:

4652

AN:

41430

American (AMR)

AF:

0.366

AC:

5575

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

911

AN:

3456

East Asian (EAS)

AF:

0.753

AC:

3812

AN:

5060

South Asian (SAS)

AF:

0.580

AC:

2787

AN:

4802

European-Finnish (FIN)

AF:

0.355

AC:

3703

AN:

10442

Middle Eastern (MID)

AF:

0.333

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.306

AC:

20616

AN:

67474

Other (OTH)

AF:

0.302

AC:

628

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1401

2801

4202

5602

7003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.287

Hom.:

895

Bravo

AF:

0.276

Asia WGS

AF:

0.558

AC:

1894

AN:

3396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.6

(source)

DANN

Benign

0.37

PhyloP100

-0.064

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over