rs7755681

Positions:

• chr6-161575338-C-T

Variant summary

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

The NM_004562.3(PRKN):​c.872-5922G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,976 control chromosomes in the GnomAD database, including 31,290 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 0.64 (31290 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.872-5922G>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.872-5922G>A		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96521 AN: 151858 Hom.: 31266 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.636 AC: 96594 AN: 151976 Hom.: 31290 Cov.: 32 AF XY: 0.636 AC XY: 47233 AN XY: 74280

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.620

Alfa AF: 0.592 Hom.: 38926

Bravo AF: 0.628

Asia WGS AF: 0.612 AC: 2132 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.56

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: rs7755681; hg19: chr6-161996370; COSMIC: COSV58266111;