rs11755155

chr6-161709447-T-G

Variant summary

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

The NM_004562.3(PRKN):c.871+76325A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,042 control chromosomes in the GnomAD database, including 16,564 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 0.46 (16564 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.871+76325A>C		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.871+76325A>C		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70019 AN: 151924 Hom.: 16539 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.461 AC: 70095 AN: 152042 Hom.: 16564 Cov.: 32 AF XY: 0.463 AC XY: 34424 AN XY: 74294

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.473

Alfa AF: 0.437 Hom.: 1837

Bravo AF: 0.472

Asia WGS AF: 0.428 AC: 1483 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.3
Dann	Benign	0.65

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: rs11755155; hg19: chr6-162130479;