Genetic Variant PCSK7:p.Leu590Leu (chr11-117207986-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_004716.4(PCSK7):c.1770T>G(p.Leu590Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 115 hom., cov: 18)

Exomes 𝑓: 0.063 ( 419 hom. )

Failed GnomAD Quality Control

Consequence

PCSK7
NM_004716.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.44

Variant links:

Genes affected

PCSK7 (HGNC:8748): (proprotein convertase subtilisin/kexin type 7) 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. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene has been implicated in the transcriptional regulation of housekeeping genes and plays a role in the regulation of iron metabolism. A t(11;14)(q23;q32) chromosome translocation associated with B-cell lymphoma occurs between this gene and its inverted counterpart. [provided by RefSeq, Feb 2014]

PCSK7 links:

ENSG00000280143 (HGNC:):

ENSG00000280143 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 11-117207986-A-C is Benign according to our data. Variant chr11-117207986-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 769808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK7	NM_004716.4 link	c.1770T>G	p.Leu590Leu	synonymous_variant	Exon 14 of 17	ENST00000320934.8	NP_004707.2	Q16549

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK7	ENST00000320934.8 link	c.1770T>G	p.Leu590Leu	synonymous_variant	Exon 14 of 17	1	NM_004716.4	ENSP00000325917.3		Q16549

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

13086

AN:

117170

Hom.:

114

Cov.:

FAILED QC

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.0126

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.0630

Gnomad EAS

AF:

0.0661

Gnomad SAS

AF:

0.0864

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.0962

Gnomad NFE

AF:

0.0530

Gnomad OTH

AF:

0.0977

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0630

AC:

26776

AN:

424750

Hom.:

419

Cov.:

AF XY:

0.0637

AC XY:

14456

AN XY:

227012

show subpopulations

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.0468

Gnomad4 ASJ exome

AF:

0.0625

Gnomad4 EAS exome

AF:

0.0582

Gnomad4 SAS exome

AF:

0.0924

Gnomad4 FIN exome

AF:

0.0696

Gnomad4 NFE exome

AF:

0.0498

Gnomad4 OTH exome

AF:

0.0682

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.112

AC:

13108

AN:

117244

Hom.:

115

Cov.:

AF XY:

0.112

AC XY:

6283

AN XY:

56190

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.0705

Gnomad4 ASJ

AF:

0.0630

Gnomad4 EAS

AF:

0.0661

Gnomad4 SAS

AF:

0.0852

Gnomad4 FIN

AF:

0.0853

Gnomad4 NFE

AF:

0.0530

Gnomad4 OTH

AF:

0.0972

Alfa

AF:

0.111

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 08, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over