rs2023048

Positions:

• chr6-162049864-C-T

Variant summary

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

The NM_004562.3(PRKN):​c.618+4227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,148 control chromosomes in the GnomAD database, including 56,310 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 0.86 (56310 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.618+4227G>A		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.618+4227G>A		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130714 AN: 152030 Hom.: 56265 Cov.: 31

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.860 AC: 130815 AN: 152148 Hom.: 56310 Cov.: 31 AF XY: 0.860 AC XY: 63976 AN XY: 74386

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.868

Alfa AF: 0.851 Hom.: 74714

Bravo AF: 0.864

Asia WGS AF: 0.843 AC: 2930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.66

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: rs2023048; hg19: chr6-162470896;