Variant 1-55058666-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGTGT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000302118.5(PCSK9):c.1503+60_1503+71del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 787 hom., cov: 0)

Exomes 𝑓: 0.083 ( 626 hom. )

Failed GnomAD Quality Control

Consequence

PCSK9
ENST00000302118.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.564

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 -16 ACMG points.

BP6

Variant 1-55058666-CGTGTGTGTGTGT-C is Benign according to our data. Variant chr1-55058666-CGTGTGTGTGTGT-C is described in ClinVar as [Likely_benign]. Clinvar id is 492238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-55058666-CGTGTGTGTGTGT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCSK9	NM_174936.4 linkuse as main transcript	c.1503+60_1503+71del		intron_variant		ENST00000302118.5	NP_777596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCSK9	ENST00000302118.5 linkuse as main transcript	c.1503+60_1503+71del		intron_variant		1	NM_174936.4	ENSP00000303208	P2	Q8NBP7-1

Frequencies

GnomAD3 genomes

AF:

0.0970

AC:

13799

AN:

142270

Hom.:

785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0975

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.0980

Gnomad MID

AF:

0.0608

Gnomad NFE

AF:

0.0942

Gnomad OTH

AF:

0.0747

GnomAD3 exomes

AF:

0.0519

AC:

7738

AN:

149146

Hom.:

AF XY:

0.0477

AC XY:

3912

AN XY:

81986

show subpopulations

Gnomad AFR exome

AF:

0.0658

Gnomad AMR exome

AF:

0.0832

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.0827

Gnomad SAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.0550

Gnomad NFE exome

AF:

0.0445

Gnomad OTH exome

AF:

0.0534

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0826

AC:

113841

AN:

1377520

Hom.:

626

AF XY:

0.0803

AC XY:

54873

AN XY:

683266

show subpopulations

Gnomad4 AFR exome

AF:

0.0877

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.0297

Gnomad4 EAS exome

AF:

0.0902

Gnomad4 SAS exome

AF:

0.0436

Gnomad4 FIN exome

AF:

0.0807

Gnomad4 NFE exome

AF:

0.0857

Gnomad4 OTH exome

AF:

0.0769

GnomAD4 genome

AF:

0.0970

AC:

13812

AN:

142352

Hom.:

787

Cov.:

AF XY:

0.0963

AC XY:

6641

AN XY:

68962

show subpopulations

Gnomad4 AFR

AF:

0.0975

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.0303

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.0446

Gnomad4 FIN

AF:

0.0980

Gnomad4 NFE

AF:

0.0942

Gnomad4 OTH

AF:

0.0737

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Oct 12, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Oct 02, 2017	- -

Hypercholesterolemia, autosomal dominant, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Familial hypercholesterolemia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Aug 05, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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