Genetic Variant PCSK7:c.1156-84G>A (chr11-117219842-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004716.4(PCSK7):c.1156-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,053,096 control chromosomes in the GnomAD database, including 113,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 24375 hom., cov: 33)

Exomes 𝑓: 0.43 ( 88850 hom. )

Consequence

PCSK7
NM_004716.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.162

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK7	NM_004716.4 link	c.1156-84G>A		intron_variant	Intron 9 of 16	ENST00000320934.8	NP_004707.2	Q16549

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK7	ENST00000320934.8 link	c.1156-84G>A		intron_variant	Intron 9 of 16	1	NM_004716.4	ENSP00000325917.3		Q16549

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81665

AN:

152048

Hom.:

24318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.679

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.499

GnomAD4 exome

AF:

0.430

AC:

387369

AN:

900930

Hom.:

88850

Cov.:

AF XY:

0.437

AC XY:

196725

AN XY:

450684

show subpopulations

Gnomad4 AFR exome

AF:

0.794

Gnomad4 AMR exome

AF:

0.590

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.704

Gnomad4 FIN exome

AF:

0.477

Gnomad4 NFE exome

AF:

0.378

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.537

AC:

81781

AN:

152166

Hom.:

24375

Cov.:

AF XY:

0.545

AC XY:

40563

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.477

Gnomad4 EAS

AF:

0.679

Gnomad4 SAS

AF:

0.720

Gnomad4 FIN

AF:

0.488

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.476

Hom.:

2358

Bravo

AF:

0.549

Asia WGS

AF:

0.718

AC:

2497

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

DANN

Benign

0.27

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over