rs7757630

Variant names:

• chr6-162519206-G-A
• rs7757630
• NM_004562.3:c.8-75733C>T

Variant summary

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

The NM_004562.3(PRKN):​c.8-75733C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,126 control chromosomes in the GnomAD database, including 660 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 0.089 (660 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.8-75733C>T		intron_variant	Intron 1 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.8-75733C>T		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13596 AN: 152008 Hom.: 661 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0810

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0831

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

GnomAD4 genome AF: 0.0894 AC: 13599 AN: 152126 Hom.: 660 Cov.: 32 AF XY: 0.0893 AC XY: 6642 AN XY: 74368

African (AFR) AF: 0.110 AC: 4551 AN: 41492

American (AMR) AF: 0.0808 AC: 1234 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.0291 AC: 150 AN: 5162

South Asian (SAS) AF: 0.170 AC: 817 AN: 4816

European-Finnish (FIN) AF: 0.0612 AC: 649 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5537 AN: 67992

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.0854 Hom.: 223

Bravo AF: 0.0891

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		0.18
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: rs7757630; hg19: chr6-162940238;