rs11966948

Positions:

• chr6-163219230-C-A
• chr6-163219230-C-G

Variant summary

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

The ENST00000366888.7(PACRG):​c.614-95597C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,992 control chromosomes in the GnomAD database, including 20,737 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 0.52 (20737 hom., cov: 32)
• Consequence: PACRG ENST00000366888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92

Genes affected

PACRG (HGNC:19152): (parkin coregulated) This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACRG	NM_001080379.2	c.614-95597C>A		intron_variant		ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7	c.614-95597C>A		intron_variant		1	NM_001080379.2	ENSP00000355854	P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79064 AN: 151874 Hom.: 20706 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.521 AC: 79132 AN: 151992 Hom.: 20737 Cov.: 32 AF XY: 0.523 AC XY: 38810 AN XY: 74270

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.527

Alfa AF: 0.531 Hom.: 4561

Bravo AF: 0.515

Asia WGS AF: 0.590 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.020
DANN	Benign	0.57

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: rs11966948; hg19: chr6-163640262;