chr6-161715127-C-T

Position:

• chr6-161715127-C-T

Variant summary

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

The ENST00000366898.6(PRKN):​c.871+70645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,138 control chromosomes in the GnomAD database, including 5,471 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 0.20 (5471 hom., cov: 33)
• Consequence: PRKN ENST00000366898.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.871+70645G>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.871+70645G>A		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29658 AN: 152020 Hom.: 5461 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.195 AC: 29704 AN: 152138 Hom.: 5471 Cov.: 33 AF XY: 0.187 AC XY: 13943 AN XY: 74394

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.0607

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0968 Hom.: 1412

Bravo AF: 0.210

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.64

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: rs11962721; hg19: chr6-162136159;