rs4383605

Variant names:

• chr4-23893586-T-G
• rs4383605
• NM_001330751.2:c.70-8655A>C

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-8655A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,092 control chromosomes in the GnomAD database, including 4,731 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 (4731 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-8655A>C		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-8655A>C		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-8655A>C		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.53-3373A>C		intron_variant	Intron 1 of 3	3
PPARGC1A	ENST00000514494.1	n.97-8655A>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32930 AN: 151976 Hom.: 4731 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.216 AC: 32926 AN: 152092 Hom.: 4731 Cov.: 33 AF XY: 0.216 AC XY: 16031 AN XY: 74384

African (AFR) AF: 0.0559 AC: 2321 AN: 41544

American (AMR) AF: 0.170 AC: 2599 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3470

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5182

South Asian (SAS) AF: 0.206 AC: 995 AN: 4824

European-Finnish (FIN) AF: 0.353 AC: 3732 AN: 10564

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21570 AN: 67924

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.278 Hom.: 8690

Bravo AF: 0.191

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	-0.88
CADD	Benign	18
DANN	Benign	0.72
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs4383605; hg19: chr4-23895209;