rs12207186

chr6-161893889-A-T

Variant summary

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

The NM_004562.3(PRKN):c.734+79413T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0632 in 152,238 control chromosomes in the GnomAD database, including 380 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 0.063 (380 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.734+79413T>A		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.734+79413T>A		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9589 AN: 152120 Hom.: 374 Cov.: 33

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0752

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

GnomAD4 genome AF: 0.0632 AC: 9615 AN: 152238 Hom.: 380 Cov.: 33 AF XY: 0.0643 AC XY: 4786 AN XY: 74440

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0515 Hom.: 36

Bravo AF: 0.0630

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.3
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: rs12207186; hg19: chr6-162314921;