1-55040059-A-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_174936.4(PCSK9):c.207+15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 38)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PCSK9
NM_174936.4 intron
NM_174936.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.224
Publications
14 publications found
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 Gene-Disease associations (from GenCC):
- hypercholesterolemia, autosomal dominant, 3Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
- homozygous familial hypercholesterolemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 1-55040059-A-T is Benign according to our data. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55040059-A-T is described in CliVar as Likely_benign. Clinvar id is 2829837.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
38
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1400786Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0AN XY: 691314
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1400786
Hom.:
Cov.:
65
AF XY:
AC XY:
0
AN XY:
691314
African (AFR)
AF:
AC:
0
AN:
31786
American (AMR)
AF:
AC:
0
AN:
36366
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25188
East Asian (EAS)
AF:
AC:
0
AN:
36038
South Asian (SAS)
AF:
AC:
0
AN:
79370
European-Finnish (FIN)
AF:
AC:
0
AN:
48728
Middle Eastern (MID)
AF:
AC:
0
AN:
4292
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1080996
Other (OTH)
AF:
AC:
0
AN:
58022
GnomAD4 genome
GnomAD4 genome
Cov.:
38
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, 3 Benign:1
Aug 20, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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