rs2970849

Variant names:

• chr4-23816184-T-C
• rs2970849
• NM_013261.5:c.878-1579A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.878-1579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,952 control chromosomes in the GnomAD database, including 12,330 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 0.39 (12330 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.878-1579A>G		intron_variant	Intron 7 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.878-1579A>G		intron_variant	Intron 7 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59782 AN: 151834 Hom.: 12314 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.394 AC: 59857 AN: 151952 Hom.: 12330 Cov.: 32 AF XY: 0.401 AC XY: 29772 AN XY: 74264

African (AFR) AF: 0.470 AC: 19458 AN: 41424

American (AMR) AF: 0.461 AC: 7041 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3466

East Asian (EAS) AF: 0.269 AC: 1381 AN: 5142

South Asian (SAS) AF: 0.360 AC: 1730 AN: 4812

European-Finnish (FIN) AF: 0.464 AC: 4901 AN: 10562

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23069 AN: 67972

Other (OTH) AF: 0.371 AC: 781 AN: 2104

Alfa AF: 0.377 Hom.: 2323

Bravo AF: 0.393

Asia WGS AF: 0.346 AC: 1200 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.95
DANN	Benign	0.51
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2970849; hg19: chr4-23817807;