rs2970872

Positions:

• chr4-23888190-A-G

Variant summary

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

The NM_013261.5(PPARGC1A):​c.54+1714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,144 control chromosomes in the GnomAD database, including 23,670 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 0.54 (23670 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

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 (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.54+1714T>C		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.54+1714T>C		intron_variant		1	NM_013261.5	ENSP00000264867	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82259 AN: 152026 Hom.: 23642 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.541 AC: 82327 AN: 152144 Hom.: 23670 Cov.: 33 AF XY: 0.526 AC XY: 39150 AN XY: 74384

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.541

Alfa AF: 0.536 Hom.: 21937

Bravo AF: 0.559

Asia WGS AF: 0.325 AC: 1133 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	0.17
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2970872; hg19: chr4-23889813;