rs16874509

Variant names:

• chr4-23994752-G-A
• rs16874509
• NM_001330751.2:c.69+96716C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23994752-G-A
• chr4-23994752-G-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+96716C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,078 control chromosomes in the GnomAD database, including 2,794 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 0.17 (2794 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 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+96716C>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.69+96716C>T		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.69+96716C>T		intron	N/A	NP_001341756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26419 AN: 151960 Hom.: 2791 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.174 AC: 26438 AN: 152078 Hom.: 2794 Cov.: 32 AF XY: 0.180 AC XY: 13386 AN XY: 74332

African (AFR) AF: 0.0849 AC: 3525 AN: 41498

American (AMR) AF: 0.307 AC: 4690 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1231 AN: 5138

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4816

European-Finnish (FIN) AF: 0.223 AC: 2367 AN: 10598

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12077 AN: 67980

Other (OTH) AF: 0.164 AC: 346 AN: 2116

Alfa AF: 0.182 Hom.: 4514

Bravo AF: 0.175

Asia WGS AF: 0.243 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.44
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs16874509; hg19: chr4-23996375;