rs2946386

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-23891956-G-C
• chr4-23891956-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330751.2(PPARGC1A):​c.70-7025C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,136 control chromosomes in the GnomAD database, including 46,348 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 0.77 (46348 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117476 AN: 152018 Hom.: 46315 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.773 AC: 117550 AN: 152136 Hom.: 46348 Cov.: 32 AF XY: 0.764 AC XY: 56799 AN XY: 74348

African (AFR) AF: 0.914 AC: 38006 AN: 41562

American (AMR) AF: 0.572 AC: 8735 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2638 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3286 AN: 5160

South Asian (SAS) AF: 0.731 AC: 3514 AN: 4808

European-Finnish (FIN) AF: 0.683 AC: 7216 AN: 10564

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51676 AN: 67980

Other (OTH) AF: 0.766 AC: 1619 AN: 2114

Alfa AF: 0.676 Hom.: 1845

Bravo AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.50
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;