rs1878949

Positions:

• chr4-23893790-A-C
• chr4-23893790-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330751.2(PPARGC1A):​c.70-8859T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,052 control chromosomes in the GnomAD database, including 5,946 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 0.24 (5946 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-8859T>G		intron_variant			NP_001317680.1
PPARGC1A	NM_001330752.2	c.19-8859T>G		intron_variant			NP_001317681.1
PPARGC1A	NM_001354825.2	c.70-8859T>G		intron_variant			NP_001341754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-3577T>G		intron_variant, non_coding_transcript_variant		3
PPARGC1A	ENST00000514494.1	n.97-8859T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36720 AN: 151934 Hom.: 5936 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.242 AC: 36763 AN: 152052 Hom.: 5946 Cov.: 33 AF XY: 0.242 AC XY: 18012 AN XY: 74350

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.232

Alfa AF: 0.151 Hom.: 2011

Bravo AF: 0.252

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1878949; hg19: chr4-23895413;