11-117207986-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004716.4(PCSK7):c.1770T>G(p.Leu590=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK7	NM_004716.4	c.1770T>G	p.Leu590=	synonymous_variant	14/17	ENST00000320934.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK7	ENST00000320934.8	c.1770T>G	p.Leu590=	synonymous_variant	14/17	1	NM_004716.4	P1
	ENST00000624094.1	n.3020A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 13086 AN: 117170 Hom.: 114 Cov.: 18 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.: 0 AF XY: 0.0637 AC XY: 14456 AN XY: 227012

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.: 18 AF XY: 0.112 AC XY: 6283 AN XY: 56190

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.: 39

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2017

- -

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

Other links and lift over

dbSNP: rs596314; hg19: chr11-117078702; COSMIC: COSV54063159; COSMIC: COSV54063159;