rs2846488

Variant names:

• chr6-162543650-C-T
• rs2846488
• NM_004562.3:c.8-100177G>A

Variant summary

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

The ENST00000366898.6(PRKN):​c.8-100177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,944 control chromosomes in the GnomAD database, including 16,917 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 0.44 (16917 hom., cov: 32)
• Consequence: PRKN ENST00000366898.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366898.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	NM_004562.3	MANE Select	c.8-100177G>A		intron	N/A	NP_004553.2
	PRKN	NM_013987.3		c.8-100177G>A		intron	N/A	NP_054642.2
	PRKN	NM_013988.3		c.8-100177G>A		intron	N/A	NP_054643.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKN	ENST00000366898.6	TSL:1 MANE Select	c.8-100177G>A		intron	N/A	ENSP00000355865.1
	PRKN	ENST00000366897.5	TSL:1	c.8-100177G>A		intron	N/A	ENSP00000355863.1
	PRKN	ENST00000366896.5	TSL:1	c.8-100177G>A		intron	N/A	ENSP00000355862.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66527 AN: 151826 Hom.: 16907 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.438 AC: 66559 AN: 151944 Hom.: 16917 Cov.: 32 AF XY: 0.432 AC XY: 32102 AN XY: 74252

African (AFR) AF: 0.218 AC: 9019 AN: 41438

American (AMR) AF: 0.433 AC: 6602 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2060 AN: 3472

East Asian (EAS) AF: 0.0354 AC: 183 AN: 5168

South Asian (SAS) AF: 0.457 AC: 2204 AN: 4820

European-Finnish (FIN) AF: 0.513 AC: 5401 AN: 10534

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39525 AN: 67942

Other (OTH) AF: 0.479 AC: 1012 AN: 2114

Alfa AF: 0.466 Hom.: 3601

Bravo AF: 0.420

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.40
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: rs2846488; hg19: chr6-162964682;