4-23824109-T-G

Variant names:

• chr4-23824109-T-G
• rs2290602
• NM_013261.5:c.877+171A>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.877+171A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 120,622 control chromosomes in the GnomAD database, including 7,116 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 0.37 (7116 hom., cov: 29)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 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.877+171A>C		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.892+171A>C		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.892+171A>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.877+171A>C		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.496+171A>C		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.*92+171A>C		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 44865 AN: 120536 Hom.: 7108 Cov.: 29

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.372 AC: 44926 AN: 120622 Hom.: 7116 Cov.: 29 AF XY: 0.376 AC XY: 22054 AN XY: 58720

African (AFR) AF: 0.410 AC: 14621 AN: 35626

American (AMR) AF: 0.435 AC: 5364 AN: 12326

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 693 AN: 2456

East Asian (EAS) AF: 0.125 AC: 449 AN: 3594

South Asian (SAS) AF: 0.298 AC: 988 AN: 3318

European-Finnish (FIN) AF: 0.425 AC: 3449 AN: 8118

Middle Eastern (MID) AF: 0.297 AC: 54 AN: 182

European-Non Finnish (NFE) AF: 0.351 AC: 18477 AN: 52656

Other (OTH) AF: 0.355 AC: 569 AN: 1604

Alfa AF: 0.512 Hom.: 5958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.44
PhyloP100		0.88
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2290602; hg19: chr4-23825732; COSMIC: COSV53529219; COSMIC: COSV53529219;