rs17576121

Positions:

• chr4-23891651-T-C

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-6720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,172 control chromosomes in the GnomAD database, including 4,683 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 0.22 (4683 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.70-6720A>G		intron_variant
PPARGC1A	NM_001330752.2	c.19-6720A>G		intron_variant
PPARGC1A	NM_001354825.2	c.70-6720A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-1438A>G		intron_variant, non_coding_transcript_variant		3
PPARGC1A	ENST00000514494.1	n.97-6720A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32768 AN: 152054 Hom.: 4683 Cov.: 33

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.215 AC: 32765 AN: 152172 Hom.: 4683 Cov.: 33 AF XY: 0.214 AC XY: 15924 AN XY: 74374

Gnomad4 AFR AF: 0.0559

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.209

Alfa AF: 0.256 Hom.: 1000

Bravo AF: 0.190

Asia WGS AF: 0.126 AC: 436 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.2
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17576121; hg19: chr4-23893274;