rs4416887

Variant names:

• chr9-75982309-A-G
• rs4416887
• NM_001372043.1:c.298-3823A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-75982309-A-G
• chr9-75982309-A-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.298-3823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,070 control chromosomes in the GnomAD database, including 39,029 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 0.71 (39029 hom., cov: 32)
• Consequence: PCSK5 NM_001372043.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK5	NM_001372043.1	c.298-3823A>G		intron_variant	Intron 2 of 37	ENST00000674117.1	NP_001358972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK5	ENST00000674117.1	c.298-3823A>G		intron_variant	Intron 2 of 37		NM_001372043.1	ENSP00000500971.1
PCSK5	ENST00000376752.9	c.298-3823A>G		intron_variant	Intron 2 of 20	1		ENSP00000365943.4
PCSK5	ENST00000545128.5	c.298-3823A>G		intron_variant	Intron 2 of 36	5		ENSP00000446280.1
PCSK5	ENST00000376767.7	n.810-3823A>G		intron_variant	Intron 2 of 13	2

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108321 AN: 151954 Hom.: 39024 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.713 AC: 108365 AN: 152070 Hom.: 39029 Cov.: 32 AF XY: 0.715 AC XY: 53127 AN XY: 74330

African (AFR) AF: 0.618 AC: 25628 AN: 41470

American (AMR) AF: 0.719 AC: 10973 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.824 AC: 4267 AN: 5176

South Asian (SAS) AF: 0.678 AC: 3269 AN: 4820

European-Finnish (FIN) AF: 0.816 AC: 8627 AN: 10576

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50682 AN: 67970

Other (OTH) AF: 0.705 AC: 1487 AN: 2108

Alfa AF: 0.727 Hom.: 21860

Bravo AF: 0.707

Asia WGS AF: 0.731 AC: 2543 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.41
PhyloP100		-1.2
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: rs4416887; hg19: chr9-78597225;