rs3821952

Positions:

• chr4-23796110-A-C

Variant summary

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

The NM_013261.5(PPARGC1A):​c.2294-185T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 152,106 control chromosomes in the GnomAD database, including 382 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 0.063 (382 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2294-185T>G		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.2294-185T>G		intron_variant		1	NM_013261.5	ENSP00000264867	P1
PPARGC1A	ENST00000613098.4	c.1913-185T>G		intron_variant		1		ENSP00000481498
PPARGC1A	ENST00000506055.5	c.*1509-185T>G		intron_variant, NMD_transcript_variant		1		ENSP00000423075
PPARGC1A	ENST00000509702.5	n.2334-185T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9594 AN: 151986 Hom.: 382 Cov.: 31

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0659

Gnomad ASJ AF: 0.0586

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0676

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

GnomAD4 genome AF: 0.0631 AC: 9597 AN: 152106 Hom.: 382 Cov.: 31 AF XY: 0.0678 AC XY: 5041 AN XY: 74364

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.0660

Gnomad4 ASJ AF: 0.0586

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0860

Gnomad4 NFE AF: 0.0432

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0487 Hom.: 173

Bravo AF: 0.0606

Asia WGS AF: 0.138 AC: 479 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.39

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: rs3821952; hg19: chr4-23797733;