rs2970870

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330751.2(PPARGC1A):​c.70-6463T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,044 control chromosomes in the GnomAD database, including 19,208 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 0.48 ( 19208 hom., cov: 32)

Consequence

PPARGC1A
NM_001330751.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.06
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPARGC1ANM_001330751.2 linkuse as main transcriptc.70-6463T>C intron_variant NP_001317680.1 Q9UBK2-3
PPARGC1ANM_001354825.2 linkuse as main transcriptc.70-6463T>C intron_variant NP_001341754.1
PPARGC1ANM_001354827.2 linkuse as main transcriptc.70-6463T>C intron_variant NP_001341756.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPARGC1AENST00000507342.5 linkuse as main transcriptn.53-1181T>C intron_variant 3
PPARGC1AENST00000514494.1 linkuse as main transcriptn.97-6463T>C intron_variant 4

Frequencies

GnomAD3 genomes
AF:
0.484
AC:
73608
AN:
151926
Hom.:
19191
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.679
Gnomad AMI
AF:
0.388
Gnomad AMR
AF:
0.365
Gnomad ASJ
AF:
0.493
Gnomad EAS
AF:
0.584
Gnomad SAS
AF:
0.402
Gnomad FIN
AF:
0.373
Gnomad MID
AF:
0.595
Gnomad NFE
AF:
0.408
Gnomad OTH
AF:
0.492
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.484
AC:
73656
AN:
152044
Hom.:
19208
Cov.:
32
AF XY:
0.481
AC XY:
35714
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.679
Gnomad4 AMR
AF:
0.365
Gnomad4 ASJ
AF:
0.493
Gnomad4 EAS
AF:
0.584
Gnomad4 SAS
AF:
0.402
Gnomad4 FIN
AF:
0.373
Gnomad4 NFE
AF:
0.408
Gnomad4 OTH
AF:
0.488
Alfa
AF:
0.429
Hom.:
23724
Bravo
AF:
0.495
Asia WGS
AF:
0.485
AC:
1687
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
8.8
DANN
Benign
0.47

Splicing

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.

Other links and lift over

dbSNP: rs2970870; hg19: chr4-23893017; API