rs7695542

Positions:

• chr4-23891250-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.70-6319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 152,164 control chromosomes in the GnomAD database, including 295 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 0.053 (295 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-6319A>G		intron_variant			NP_001317680.1
PPARGC1A	NM_001330752.2	c.19-6319A>G		intron_variant			NP_001317681.1
PPARGC1A	NM_001354825.2	c.70-6319A>G		intron_variant			NP_001341754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-1037A>G		intron_variant, non_coding_transcript_variant		3
PPARGC1A	ENST00000514494.1	n.97-6319A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8031 AN: 152046 Hom.: 293 Cov.: 31

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0451

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

GnomAD4 genome AF: 0.0529 AC: 8048 AN: 152164 Hom.: 295 Cov.: 31 AF XY: 0.0497 AC XY: 3701 AN XY: 74400

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0295

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.0431

Gnomad4 OTH AF: 0.0446

Alfa AF: 0.0592 Hom.: 56

Bravo AF: 0.0563

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.3
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7695542; hg19: chr4-23892873;