rs2276201

chr6-162728465-T-C

Variant summary

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

The NM_001080379.2(PACRG):c.156+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,551,346 control chromosomes in the GnomAD database, including 80,048 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 0.40 (15141 hom., cov: 31)
  • Exomes 𝑓: 0.29 (64907 hom.)
• Consequence: PACRG NM_001080379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601

Genes affected

PACRG (HGNC:19152): (parkin coregulated) This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PACRG	NM_001080379.2	c.156+74T>C		intron_variant		ENST00000366888.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PACRG	ENST00000366888.7	c.156+74T>C		intron_variant		1	NM_001080379.2	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61390 AN: 151778 Hom.: 15122 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.294 AC: 411451 AN: 1399450 Hom.: 64907 AF XY: 0.293 AC XY: 203093 AN XY: 693576

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.405 AC: 61444 AN: 151896 Hom.: 15141 Cov.: 31 AF XY: 0.400 AC XY: 29670 AN XY: 74238

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.391

Alfa AF: 0.305 Hom.: 12307

Bravo AF: 0.436

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.1
Dann	Benign	0.64

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: rs2276201; hg19: chr6-163149497; COSMIC: COSV58234229; COSMIC: COSV58234229;