rs4550905

Positions:

• chr4-23873936-G-A
• chr4-23873936-G-C
• chr4-23873936-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.234+10816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,044 control chromosomes in the GnomAD database, including 30,478 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 0.63 (30478 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+10816C>T		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+10816C>T		intron_variant		1	NM_013261.5	ENSP00000264867	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95313 AN: 151924 Hom.: 30487 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.627 AC: 95333 AN: 152044 Hom.: 30478 Cov.: 32 AF XY: 0.626 AC XY: 46486 AN XY: 74306

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.628

Alfa AF: 0.679 Hom.: 18793

Bravo AF: 0.612

Asia WGS AF: 0.652 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs4550905; hg19: chr4-23875559;