rs495991

Positions:

• chr6-161534405-A-G

Variant summary

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

The NM_004562.3(PRKN):​c.1083+14449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,142 control chromosomes in the GnomAD database, including 53,850 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 0.84 (53850 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.1083+14449T>C		intron_variant		ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.1083+14449T>C		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127597 AN: 152024 Hom.: 53790 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.839 AC: 127714 AN: 152142 Hom.: 53850 Cov.: 32 AF XY: 0.837 AC XY: 62215 AN XY: 74350

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.833

Alfa AF: 0.844 Hom.: 43891

Bravo AF: 0.829

Asia WGS AF: 0.757 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.86
DANN	Benign	0.27

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: rs495991; hg19: chr6-161955437; COSMIC: COSV58265626;