rs12190800

Positions:

• chr6-161507492-C-T

Variant summary

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

The ENST00000366898.6(PRKN):​c.1083+41362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,972 control chromosomes in the GnomAD database, including 3,367 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 0.19 (3367 hom., cov: 32)
• Consequence: PRKN ENST00000366898.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.1083+41362G>A		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+41362G>A		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28827 AN: 151854 Hom.: 3357 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00484

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.190 AC: 28865 AN: 151972 Hom.: 3367 Cov.: 32 AF XY: 0.186 AC XY: 13818 AN XY: 74280

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00485

Gnomad4 SAS AF: 0.0875

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.176

Alfa AF: 0.164 Hom.: 592

Bravo AF: 0.193

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.69

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: rs12190800; hg19: chr6-161928524;