rs737631

Variant names:

• chr6-161741401-G-A
• rs737631
• NM_004562.3:c.871+44371C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.871+44371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,038 control chromosomes in the GnomAD database, including 6,382 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 0.28 (6382 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• Publications: 3 publications found

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]

PRKN Gene-Disease associations (from GenCC):

• autosomal recessive juvenile Parkinson disease 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.871+44371C>T		intron_variant	Intron 7 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.871+44371C>T		intron_variant	Intron 7 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43036 AN: 151920 Hom.: 6375 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0766

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.283 AC: 43075 AN: 152038 Hom.: 6382 Cov.: 33 AF XY: 0.281 AC XY: 20870 AN XY: 74310

African (AFR) AF: 0.237 AC: 9823 AN: 41480

American (AMR) AF: 0.317 AC: 4842 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3466

East Asian (EAS) AF: 0.0765 AC: 396 AN: 5174

South Asian (SAS) AF: 0.179 AC: 864 AN: 4816

European-Finnish (FIN) AF: 0.348 AC: 3676 AN: 10570

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21471 AN: 67954

Other (OTH) AF: 0.280 AC: 589 AN: 2104

Alfa AF: 0.296 Hom.: 1064

Bravo AF: 0.282

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.80
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs737631; hg19: chr6-162162433; COSMIC: COSV58266745;