rs6937817

Positions:

• chr6-161496305-T-C
• chr6-161496305-T-G

Variant summary

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

The ENST00000366898.6(PRKN):​c.1083+52549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,158 control chromosomes in the GnomAD database, including 22,425 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 0.52 (22425 hom., cov: 33)
• Consequence: PRKN ENST00000366898.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.1083+52549A>G		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+52549A>G		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78409 AN: 152040 Hom.: 22384 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.516 AC: 78504 AN: 152158 Hom.: 22425 Cov.: 33 AF XY: 0.505 AC XY: 37561 AN XY: 74388

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.498

Alfa AF: 0.382 Hom.: 1598

Bravo AF: 0.531

Asia WGS AF: 0.277 AC: 964 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	2.6
DANN	Benign	0.46

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: rs6937817; hg19: chr6-161917337; COSMIC: COSV58264964;