Variant rs2290604 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_013261.5(PPARGC1A):c.553-11T>C variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0818 in 1,612,744 control chromosomes in the GnomAD database, including 6,241 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 0.084 ( 603 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5638 hom. )

Consequence

PPARGC1A
NM_013261.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.1777

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.13

Variant links:

Genes affected

PPARGC1A (HGNC:9237): (PPARG coactivator 1 alpha) The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]

PPARGC1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5 linkuse as main transcript	c.553-11T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7 linkuse as main transcript	c.553-11T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_013261.5	P1	Q9UBK2-1

Frequencies

GnomAD3 genomes

AF:

0.0842

AC:

12798

AN:

152058

Hom.:

604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0597

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.0997

Gnomad ASJ

AF:

0.0997

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.0923

GnomAD3 exomes

AF:

0.100

AC:

25218

AN:

251006

Hom.:

1458

AF XY:

0.101

AC XY:

13759

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.0551

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0815

AC:

119102

AN:

1460568

Hom.:

5638

Cov.:

AF XY:

0.0833

AC XY:

60555

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.0561

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.0991

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.0700

Gnomad4 OTH exome

AF:

0.0892

GnomAD4 genome

AF:

0.0841

AC:

12794

AN:

152176

Hom.:

603

Cov.:

AF XY:

0.0895

AC XY:

6655

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0595

Gnomad4 AMR

AF:

0.0998

Gnomad4 ASJ

AF:

0.0997

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0742

Gnomad4 OTH

AF:

0.0908

Alfa

AF:

0.0733

Hom.:

164

Bravo

AF:

0.0792

Asia WGS

AF:

0.145

AC:

502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.18

dbscSNV1_RF

Benign

0.38

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over