rs6832344

Variant names:

• chr4-24055913-A-G
• rs6832344
• NM_001330751.2:c.69+35555T>C

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+35555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,176 control chromosomes in the GnomAD database, including 10,299 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 0.36 (10299 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.69+35555T>C		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.69+35555T>C		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.69+35555T>C		intron_variant	Intron 2 of 13		NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54519 AN: 152058 Hom.: 10298 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.358 AC: 54541 AN: 152176 Hom.: 10299 Cov.: 33 AF XY: 0.358 AC XY: 26660 AN XY: 74412

African (AFR) AF: 0.243 AC: 10080 AN: 41518

American (AMR) AF: 0.383 AC: 5860 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1455 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2204 AN: 5170

South Asian (SAS) AF: 0.436 AC: 2102 AN: 4820

European-Finnish (FIN) AF: 0.354 AC: 3748 AN: 10592

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27812 AN: 67994

Other (OTH) AF: 0.388 AC: 822 AN: 2116

Alfa AF: 0.380 Hom.: 4408

Bravo AF: 0.356

Asia WGS AF: 0.421 AC: 1463 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.26
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs6832344; hg19: chr4-24057536;