rs640050

Variant names:

• chr4-24046063-A-G
• rs640050
• NM_001330751.2:c.69+45405T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-24046063-A-G
• chr4-24046063-A-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.69+45405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,014 control chromosomes in the GnomAD database, including 21,313 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 0.52 (21313 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 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.69+45405T>C		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.69+45405T>C		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.69+45405T>C		intron	N/A	NP_001341756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79296 AN: 151896 Hom.: 21318 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.522 AC: 79318 AN: 152014 Hom.: 21313 Cov.: 32 AF XY: 0.520 AC XY: 38602 AN XY: 74274

African (AFR) AF: 0.402 AC: 16696 AN: 41496

American (AMR) AF: 0.506 AC: 7736 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2001 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2049 AN: 5140

South Asian (SAS) AF: 0.443 AC: 2129 AN: 4806

European-Finnish (FIN) AF: 0.602 AC: 6364 AN: 10568

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40625 AN: 67948

Other (OTH) AF: 0.524 AC: 1104 AN: 2106

Alfa AF: 0.563 Hom.: 56087

Bravo AF: 0.509

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.60
PhyloP100		0.68

Splicing

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

Other links and lift over

dbSNP: rs640050; hg19: chr4-24047686;