rs4091546

chr6-162573161-G-C

Variant summary

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

The NM_004562.3(PRKN):c.8-129688C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,008 control chromosomes in the GnomAD database, including 4,574 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 0.22 (4574 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.8-129688C>G		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.8-129688C>G		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33989 AN: 151890 Hom.: 4567 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.224 AC: 34019 AN: 152008 Hom.: 4574 Cov.: 32 AF XY: 0.224 AC XY: 16635 AN XY: 74316

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.202

Alfa AF: 0.205 Hom.: 454

Bravo AF: 0.234

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	11
Dann	Benign	0.76

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: rs4091546; hg19: chr6-162994193;