11-117207963-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004716.4(PCSK7):c.1786+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (338 hom., cov: 18)
  • Exomes 𝑓: 0.085 (1448 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCSK7 NM_004716.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001995
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.200

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-117207963-G-A is Benign according to our data. Variant chr11-117207963-G-A is described in ClinVar as [Benign]. Clinvar id is 769807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK7	NM_004716.4	c.1786+7C>T		splice_region_variant, intron_variant		ENST00000320934.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK7	ENST00000320934.8	c.1786+7C>T		splice_region_variant, intron_variant		1	NM_004716.4	P1
	ENST00000624094.1	n.2997G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15297 AN: 119918 Hom.: 337 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0173

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.0850 AC: 35408 AN: 416772 Hom.: 1448 Cov.: 0 AF XY: 0.0860 AC XY: 19218 AN XY: 223430

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.0623

Gnomad4 ASJ exome AF: 0.0929

Gnomad4 EAS exome AF: 0.0905

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0876

Gnomad4 NFE exome AF: 0.0726

Gnomad4 OTH exome AF: 0.0874

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.128 AC: 15315 AN: 119996 Hom.: 338 Cov.: 18 AF XY: 0.126 AC XY: 7269 AN XY: 57538

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0789

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0648 Hom.: 54

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.9
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs202087066; hg19: chr11-117078679; COSMIC: COSV54063076; COSMIC: COSV54063076;