rs1878949

Variant names:

• chr4-23893790-A-C
• rs1878949
• NM_001330751.2:c.70-8859T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-8859T>G		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-8859T>G		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-8859T>G		intron_variant	Intron 2 of 13		NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-3577T>G		intron_variant	Intron 1 of 3	3
PPARGC1A	ENST00000514494.1	n.97-8859T>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.455 AC: 18841 AN: 41438

American (AMR) AF: 0.163 AC: 2483 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 709 AN: 3466

East Asian (EAS) AF: 0.371 AC: 1919 AN: 5168

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1718 AN: 10600

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9348 AN: 67966

Other (OTH) AF: 0.232 AC: 491 AN: 2114

Alfa AF: 0.166 Hom.: 3384

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
PhyloP100		2.5

Splicing

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

Other links and lift over

dbSNP: rs1878949; hg19: chr4-23895413;