rs4919611

chr10-102135182-C-Achr10-102135182-C-Gchr10-102135182-C-T

Variant summary

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

The NM_015062.5(PPRC1):c.153+1961C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,234 control chromosomes in the GnomAD database, including 62,325 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 0.90 (62325 hom., cov: 31)
• Consequence: PPRC1 NM_015062.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743

Genes affected

PPRC1 (HGNC:30025): (PPARG related coactivator 1) The protein encoded by this gene is similar to PPAR-gamma coactivator 1 (PPARGC1/PGC-1), a protein that can activate mitochondrial biogenesis in part through a direct interaction with nuclear respiratory factor 1 (NRF1). This protein has been shown to interact with NRF1. It is thought to be a functional relative of PPAR-gamma coactivator 1 that activates mitochondrial biogenesis through NRF1 in response to proliferative signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPRC1	NM_015062.5	c.153+1961C>A		intron_variant		ENST00000278070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPRC1	ENST00000278070.7	c.153+1961C>A		intron_variant		1	NM_015062.5	P2
PPRC1	ENST00000413464.6	c.153+1961C>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137421 AN: 152116 Hom.: 62263 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.903 AC: 137541 AN: 152234 Hom.: 62325 Cov.: 31 AF XY: 0.902 AC XY: 67150 AN XY: 74418

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.941

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.872

Alfa AF: 0.881 Hom.: 33975

Bravo AF: 0.904

Asia WGS AF: 0.873 AC: 3034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	4.7
Dann	Benign	0.55

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: rs4919611; hg19: chr10-103894939;