rs17576121

Variant names:

• chr4-23891651-T-C
• rs17576121
• NM_001330751.2:c.70-6720A>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.70-6720A>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
• Publications: 10 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=-0.74).
• 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 rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-6720A>G		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-6720A>G		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-6720A>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.53-1438A>G		intron_variant	Intron 1 of 3	3
PPARGC1A	ENST00000514494.1	n.97-6720A>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.0559 AC: 2321 AN: 41546

American (AMR) AF: 0.170 AC: 2595 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3466

East Asian (EAS) AF: 0.0299 AC: 155 AN: 5178

South Asian (SAS) AF: 0.207 AC: 997 AN: 4824

European-Finnish (FIN) AF: 0.345 AC: 3645 AN: 10566

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21500 AN: 67996

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.251 Hom.: 1004

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
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs17576121; hg19: chr4-23893274;