rs2970865

Positions:

• chr4-23893931-G-A
• chr4-23893931-G-C

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-9000C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,990 control chromosomes in the GnomAD database, including 47,477 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 0.78 (47477 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.70-9000C>T		intron_variant
PPARGC1A	NM_001330752.2	c.19-9000C>T		intron_variant
PPARGC1A	NM_001354825.2	c.70-9000C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-3718C>T		intron_variant, non_coding_transcript_variant		3
PPARGC1A	ENST00000514494.1	n.97-9000C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118644 AN: 151872 Hom.: 47440 Cov.: 31

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.781 AC: 118720 AN: 151990 Hom.: 47477 Cov.: 31 AF XY: 0.771 AC XY: 57276 AN XY: 74306

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.771

Alfa AF: 0.754 Hom.: 3220

Bravo AF: 0.772

Asia WGS AF: 0.606 AC: 2110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2970865; hg19: chr4-23895554;