rs11144766

Variant names:

• chr9-76150085-C-T
• rs11144766
• NM_001372043.1:c.1313-6960C>T

Variant summary

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

The NM_001372043.1(PCSK5):​c.1313-6960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 151,992 control chromosomes in the GnomAD database, including 2,400 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 0.17 (2400 hom., cov: 32)
• Consequence: PCSK5 NM_001372043.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 4 publications found

Genes affected

PCSK5 (HGNC:8747): (proprotein convertase subtilisin/kexin type 5) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER. It then sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. This encoded protein is widely expressed and one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It mediates posttranslational endoproteolytic processing for several integrin alpha subunits and is thought to process prorenin, pro-membrane type-1 matrix metalloproteinase and HIV-1 glycoprotein gp160. Alternative splicing results in multiple transcript variants, some of which encode distinct isoforms, including a protease packaged into dense core granules (PC5A) and a type 1 membrane bound protease (PC5B). [provided by RefSeq, May 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372043.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK5	NM_001372043.1	MANE Select	c.1313-6960C>T		intron	N/A	NP_001358972.1
	PCSK5	NM_001190482.2		c.1313-6960C>T		intron	N/A	NP_001177411.1
	PCSK5	NM_006200.6		c.1313-6960C>T		intron	N/A	NP_006191.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK5	ENST00000674117.1	MANE Select	c.1313-6960C>T		intron	N/A	ENSP00000500971.1
	PCSK5	ENST00000376752.9	TSL:1	c.1313-6960C>T		intron	N/A	ENSP00000365943.4
	PCSK5	ENST00000854198.1		c.1313-6960C>T		intron	N/A	ENSP00000524257.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25790 AN: 151874 Hom.: 2397 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.170 AC: 25799 AN: 151992 Hom.: 2400 Cov.: 32 AF XY: 0.168 AC XY: 12495 AN XY: 74276

African (AFR) AF: 0.151 AC: 6250 AN: 41428

American (AMR) AF: 0.125 AC: 1908 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1603 AN: 5168

South Asian (SAS) AF: 0.135 AC: 650 AN: 4822

European-Finnish (FIN) AF: 0.178 AC: 1880 AN: 10538

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12177 AN: 67968

Other (OTH) AF: 0.184 AC: 390 AN: 2114

Alfa AF: 0.175 Hom.: 2810

Bravo AF: 0.169

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-1.1
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: rs11144766; hg19: chr9-78765001;