11-117207963-G-A

Variant names:

• chr11-117207963-G-A
• rs202087066
• NM_004716.4:c.1786+7C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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]

ENSG00000280143 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
PCSK7	NM_004716.4	c.1786+7C>T		splice_region_variant, intron_variant	Intron 14 of 16	ENST00000320934.8	NP_004707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK7	ENST00000320934.8	c.1786+7C>T		splice_region_variant, intron_variant	Intron 14 of 16	1	NM_004716.4	ENSP00000325917.3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 15297 AN: 119918 Hom.: 337 Cov.: 18

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

GnomAD2 exomes AF: 0.0956 AC: 8181 AN: 85562 AF XY: 0.0946

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.0756

Gnomad NFE exome AF: 0.0767

Gnomad OTH exome AF: 0.0868

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 AC: 2558 AN: 10464

Gnomad4 AMR exome AF: 0.0623 AC: 1665 AN: 26712

Gnomad4 ASJ exome AF: 0.0929 AC: 1206 AN: 12982

Gnomad4 EAS exome AF: 0.0905 AC: 1515 AN: 16740

Gnomad4 SAS exome AF: 0.121 AC: 5439 AN: 45102

Gnomad4 FIN exome AF: 0.0876 AC: 3259 AN: 37202

Gnomad4 NFE exome AF: 0.0726 AC: 17709 AN: 244028

Gnomad4 Remaining exome AF: 0.0874 AC: 1917 AN: 21926

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 AC: 0.256948 AN: 0.256948

Gnomad4 AMR AF: 0.0789 AC: 0.0789113 AN: 0.0789113

Gnomad4 ASJ AF: 0.107 AC: 0.106643 AN: 0.106643

Gnomad4 EAS AF: 0.102 AC: 0.102374 AN: 0.102374

Gnomad4 SAS AF: 0.105 AC: 0.104606 AN: 0.104606

Gnomad4 FIN AF: 0.115 AC: 0.115376 AN: 0.115376

Gnomad4 NFE AF: 0.0789 AC: 0.0789331 AN: 0.0789331

Gnomad4 OTH AF: 0.107 AC: 0.107098 AN: 0.107098

Alfa AF: 0.0648 Hom.: 54

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 08, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.82
CADD	Benign	4.9
DANN	Benign	0.62
Mutation Taster		=100/0	polymorphism (auto)

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;