rs2970872

Variant names:

• chr4-23888190-A-G
• rs2970872
• NM_013261.5:c.54+1714T>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+1714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,144 control chromosomes in the GnomAD database, including 23,670 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 0.54 (23670 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.54+1714T>C		intron_variant	Intron 1 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.54+1714T>C		intron_variant	Intron 1 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82259 AN: 152026 Hom.: 23642 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.541 AC: 82327 AN: 152144 Hom.: 23670 Cov.: 33 AF XY: 0.526 AC XY: 39150 AN XY: 74384

African (AFR) AF: 0.712 AC: 29530 AN: 41492

American (AMR) AF: 0.434 AC: 6639 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1867 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5166

South Asian (SAS) AF: 0.405 AC: 1949 AN: 4814

European-Finnish (FIN) AF: 0.322 AC: 3414 AN: 10590

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35959 AN: 67992

Other (OTH) AF: 0.541 AC: 1144 AN: 2114

Alfa AF: 0.536 Hom.: 32654

Bravo AF: 0.559

Asia WGS AF: 0.325 AC: 1133 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.46
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2970872; hg19: chr4-23889813;