rs1884158

Variant names:

• chr6-161740634-C-T
• rs1884158
• NM_004562.3:c.871+45138G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.871+45138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,148 control chromosomes in the GnomAD database, including 6,095 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 0.28 (6095 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 8 publications found

Genes affected

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PRKN Gene-Disease associations (from GenCC):

• autosomal recessive juvenile Parkinson disease 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.871+45138G>A		intron_variant	Intron 7 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.871+45138G>A		intron_variant	Intron 7 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42062 AN: 152032 Hom.: 6093 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0786

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.277 AC: 42080 AN: 152148 Hom.: 6095 Cov.: 33 AF XY: 0.274 AC XY: 20387 AN XY: 74378

African (AFR) AF: 0.224 AC: 9314 AN: 41502

American (AMR) AF: 0.309 AC: 4720 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3470

East Asian (EAS) AF: 0.0785 AC: 407 AN: 5182

South Asian (SAS) AF: 0.178 AC: 860 AN: 4822

European-Finnish (FIN) AF: 0.347 AC: 3673 AN: 10584

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21103 AN: 67986

Other (OTH) AF: 0.273 AC: 575 AN: 2110

Alfa AF: 0.293 Hom.: 15869

Bravo AF: 0.275

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.81
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs1884158; hg19: chr6-162161666; COSMIC: COSV58266737;