Variant rs483462 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_174936.4(PCSK9):c.1681+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,526,076 control chromosomes in the GnomAD database, including 374,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.63 ( 32361 hom., cov: 34)

Exomes 𝑓: 0.70 ( 341704 hom. )

Consequence

PCSK9
NM_174936.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.58

Variant links:

Genes affected

PCSK9 (HGNC:20001): (proprotein convertase subtilisin/kexin type 9) 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. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

PCSK9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 1-55059727-G-A is Benign according to our data. Variant chr1-55059727-G-A is described in ClinVar as [Benign]. Clinvar id is 265948.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55059727-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK9	NM_174936.4 linkuse as main transcript	c.1681+64G>A		intron_variant		ENST00000302118.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK9	ENST00000302118.5 linkuse as main transcript	c.1681+64G>A		intron_variant		1	NM_174936.4	P2	Q8NBP7-1

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96354

AN:

152022

Hom.:

32358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.775

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.702

Gnomad OTH

AF:

0.681

GnomAD4 exome

AF:

0.702

AC:

965006

AN:

1373936

Hom.:

341704

AF XY:

0.705

AC XY:

476105

AN XY:

675774

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.828

Gnomad4 ASJ exome

AF:

0.625

Gnomad4 EAS exome

AF:

0.860

Gnomad4 SAS exome

AF:

0.753

Gnomad4 FIN exome

AF:

0.721

Gnomad4 NFE exome

AF:

0.700

Gnomad4 OTH exome

AF:

0.689

GnomAD4 genome

AF:

0.633

AC:

96377

AN:

152140

Hom.:

32361

Cov.:

AF XY:

0.641

AC XY:

47648

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.776

Gnomad4 ASJ

AF:

0.628

Gnomad4 EAS

AF:

0.859

Gnomad4 SAS

AF:

0.765

Gnomad4 FIN

AF:

0.719

Gnomad4 NFE

AF:

0.702

Gnomad4 OTH

AF:

0.683

Alfa

AF:

0.672

Hom.:

14097

Bravo

AF:

0.627

Asia WGS

AF:

0.771

AC:

2679

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Benign:1

Benign, criteria provided, single submitter

research

Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge

Mar 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0050

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over