rs2156745

Positions:

• chr6-162016355-C-A

Variant summary

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

The NM_004562.3(PRKN):​c.618+37736G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,936 control chromosomes in the GnomAD database, including 4,440 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 0.23 (4440 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.618+37736G>T		intron_variant		ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.618+37736G>T		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34508 AN: 151818 Hom.: 4438 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.0479

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.227 AC: 34520 AN: 151936 Hom.: 4440 Cov.: 31 AF XY: 0.222 AC XY: 16448 AN XY: 74256

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.0478

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.240

Alfa AF: 0.284 Hom.: 8416

Bravo AF: 0.219

Asia WGS AF: 0.138 AC: 482 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	0.039
DANN	Benign	0.45

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: rs2156745; hg19: chr6-162437387; COSMIC: COSV58209636;