rs1954916

Variant names:

• chr6-162026580-T-C
• rs1954916
• NM_004562.3:c.618+27511A>G

Variant summary

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

The NM_004562.3(PRKN):​c.618+27511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,240 control chromosomes in the GnomAD database, including 2,169 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 0.17 (2169 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.618+27511A>G		intron_variant	Intron 5 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.618+27511A>G		intron_variant	Intron 5 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25433 AN: 152122 Hom.: 2171 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.167 AC: 25426 AN: 152240 Hom.: 2169 Cov.: 32 AF XY: 0.168 AC XY: 12497 AN XY: 74454

African (AFR) AF: 0.132 AC: 5463 AN: 41528

American (AMR) AF: 0.188 AC: 2872 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3472

East Asian (EAS) AF: 0.141 AC: 730 AN: 5188

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1547 AN: 10606

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12138 AN: 68012

Other (OTH) AF: 0.189 AC: 400 AN: 2114

Alfa AF: 0.176 Hom.: 9772

Bravo AF: 0.168

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.86
PhyloP100		-0.065
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: rs1954916; hg19: chr6-162447612;