rs900414

Variant names:

• chr15-101314378-A-G
• rs900414
• NM_002570.5:c.2570-873T>C

Variant summary

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

The NM_002570.5(PCSK6):​c.2570-873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,094 control chromosomes in the GnomAD database, including 18,100 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 0.43 (18100 hom., cov: 33)
• Consequence: PCSK6 NM_002570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 6 publications found

Genes affected

PCSK6 (HGNC:8569): (proprotein convertase subtilisin/kexin type 6) 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 and sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK6	NM_002570.5	c.2570-873T>C		intron_variant	Intron 19 of 21	ENST00000611716.5	NP_002561.1
PCSK6	NM_138319.4	c.2531-873T>C		intron_variant	Intron 18 of 20		NP_612192.1
PCSK6	NM_001291309.2	c.2348-873T>C		intron_variant	Intron 17 of 19		NP_001278238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK6	ENST00000611716.5	c.2570-873T>C		intron_variant	Intron 19 of 21	1	NM_002570.5	ENSP00000482760.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65274 AN: 151976 Hom.: 18063 Cov.: 33

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.430 AC: 65371 AN: 152094 Hom.: 18100 Cov.: 33 AF XY: 0.422 AC XY: 31414 AN XY: 74388

African (AFR) AF: 0.798 AC: 33088 AN: 41472

American (AMR) AF: 0.376 AC: 5748 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3464

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5182

South Asian (SAS) AF: 0.321 AC: 1544 AN: 4816

European-Finnish (FIN) AF: 0.205 AC: 2168 AN: 10596

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19607 AN: 67958

Other (OTH) AF: 0.429 AC: 908 AN: 2116

Alfa AF: 0.360 Hom.: 8082

Bravo AF: 0.458

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		0.0060
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: rs900414; hg19: chr15-101854583;