Variant 11-117207963-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PCSK7	NM_004716.4 linkuse as main transcript	c.1786+7C>T		splice_region_variant, intron_variant		ENST00000320934.8	NP_004707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCSK7	ENST00000320934.8 linkuse as main transcript	c.1786+7C>T		splice_region_variant, intron_variant		1	NM_004716.4	ENSP00000325917	P1
	ENST00000624094.1 linkuse as main transcript	n.2997G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

15297

AN:

119918

Hom.:

337

Cov.:

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.:

AF XY:

0.0860

AC XY:

19218

AN XY:

223430

show subpopulations

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.:

AF XY:

0.126

AC XY:

7269

AN XY:

57538

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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