NM_001330751.2:c.70-6815A>G

Variant names:

• chr4-23891746-T-C
• rs2970869
• NM_001330751.2:c.70-6815A>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.70-6815A>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
• Publications: 9 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 (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

African (AFR) AF: 0.928 AC: 38538 AN: 41530

American (AMR) AF: 0.584 AC: 8930 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2642 AN: 3472

East Asian (EAS) AF: 0.619 AC: 3205 AN: 5180

South Asian (SAS) AF: 0.732 AC: 3529 AN: 4824

European-Finnish (FIN) AF: 0.734 AC: 7756 AN: 10560

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52816 AN: 67968

Other (OTH) AF: 0.778 AC: 1642 AN: 2110

Alfa AF: 0.777 Hom.: 23307

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
PhyloP100		0.040

Splicing

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

Other links and lift over

dbSNP: rs2970869; hg19: chr4-23893369;