4-23891746-T-C

Variant names:

• chr4-23891746-T-C
• rs2970869
• NM_001330751.2:c.70-6815A>G

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-6815A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,128 control chromosomes in the GnomAD database, including 48,244 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 0.79 (48244 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.88).
• 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 rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-6815A>G		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-6815A>G		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-6815A>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.53-1533A>G		intron_variant	Intron 1 of 3	3
PPARGC1A	ENST00000514494.1	n.97-6815A>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119864 AN: 152010 Hom.: 48203 Cov.: 33

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.788 AC: 119945 AN: 152128 Hom.: 48244 Cov.: 33 AF XY: 0.781 AC XY: 58045 AN XY: 74364

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.778

Alfa AF: 0.775 Hom.: 20588

Bravo AF: 0.778

Asia WGS AF: 0.681 AC: 2371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2970869; hg19: chr4-23893369;