rs2970852

Positions:

• chr4-23819900-C-T

Variant summary

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

The NM_013261.5(PPARGC1A):​c.877+4380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,950 control chromosomes in the GnomAD database, including 5,232 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 0.25 (5232 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.877+4380G>A		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.877+4380G>A		intron_variant		1	NM_013261.5	ENSP00000264867	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38275 AN: 151832 Hom.: 5230 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.252 AC: 38318 AN: 151950 Hom.: 5232 Cov.: 32 AF XY: 0.254 AC XY: 18880 AN XY: 74252

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.237

Alfa AF: 0.278 Hom.: 753

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2970852; hg19: chr4-23821523;