NM_001330751.2:c.70-7025C>A

Variant names:

• chr4-23891956-G-T
• rs2946386
• NM_001330751.2:c.70-7025C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001330751.2(PPARGC1A):​c.70-7025C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 152,176 control chromosomes in the GnomAD database, including 43 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 0.022 (43 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.674
• 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=-0.83).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0223 (3398/152176) while in subpopulation AFR AF = 0.0341 (1416/41566). AF 95% confidence interval is 0.0326. There are 43 homozygotes in GnomAd4. There are 1726 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3398 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330751.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_001330751.2		c.70-7025C>A		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.70-7025C>A		intron	N/A	NP_001341754.1	Q9UBK2-3
	PPARGC1A	NM_001354827.2		c.70-7025C>A		intron	N/A	NP_001341756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000507342.5	TSL:3	n.53-1743C>A		intron	N/A
	PPARGC1A	ENST00000514494.1	TSL:4	n.97-7025C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3387 AN: 152058 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0223 AC: 3398 AN: 152176 Hom.: 43 Cov.: 32 AF XY: 0.0232 AC XY: 1726 AN XY: 74370

African (AFR) AF: 0.0341 AC: 1416 AN: 41566

American (AMR) AF: 0.0141 AC: 216 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4814

European-Finnish (FIN) AF: 0.0521 AC: 551 AN: 10570

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1143 AN: 67988

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Alfa AF: 0.0164 Hom.: 1845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.30
PhyloP100		0.67

Splicing

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

Other links and lift over

dbSNP: rs2946386; hg19: chr4-23893579;