NM_013261.5:c.54+1746T>C

Variant names:

• chr4-23888158-A-G
• rs2970873
• NM_013261.5:c.54+1746T>C

Variant summary

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

The NM_013261.5(PPARGC1A):​c.54+1746T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,232 control chromosomes in the GnomAD database, including 56,355 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 0.86 (56355 hom., cov: 34)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 8 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 = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013261.5. 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_013261.5	MANE Select	c.54+1746T>C		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.70-3227T>C		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.70-3227T>C		intron	N/A	NP_001341754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.54+1746T>C		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000506055.5	TSL:1	n.54+1746T>C		intron	N/A	ENSP00000423075.1
	PPARGC1A	ENST00000513205.5	TSL:1	n.54+1746T>C		intron	N/A	ENSP00000421632.1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130218 AN: 152114 Hom.: 56309 Cov.: 34

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.856 AC: 130310 AN: 152232 Hom.: 56355 Cov.: 34 AF XY: 0.848 AC XY: 63066 AN XY: 74400

African (AFR) AF: 0.965 AC: 40118 AN: 41564

American (AMR) AF: 0.740 AC: 11324 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2838 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3487 AN: 5156

South Asian (SAS) AF: 0.761 AC: 3671 AN: 4822

European-Finnish (FIN) AF: 0.758 AC: 8015 AN: 10578

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.853 AC: 58049 AN: 68024

Other (OTH) AF: 0.847 AC: 1792 AN: 2116

Alfa AF: 0.846 Hom.: 23740

Bravo AF: 0.859

Asia WGS AF: 0.737 AC: 2563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.048
DANN	Benign	0.24
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2970873; hg19: chr4-23889781;