1-55058666-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGT
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_174936.4(PCSK9):c.1503+54_1503+71delGTGTGTGTGTGTGTGTGT 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 0.063 ( 417 hom., cov: 0)
Exomes 𝑓: 0.037 ( 109 hom. )
Failed GnomAD Quality Control
Consequence
PCSK9
NM_174936.4 intron
NM_174936.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.564
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 1-55058666-CGTGTGTGTGTGTGTGTGT-C is Benign according to our data. Variant chr1-55058666-CGTGTGTGTGTGTGTGTGT-C is described in ClinVar as [Likely_benign]. Clinvar id is 492235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-55058666-CGTGTGTGTGTGTGTGTGT-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0633 AC: 9006AN: 142358Hom.: 418 Cov.: 0
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GnomAD3 exomes AF: 0.0361 AC: 5378AN: 149146Hom.: 141 AF XY: 0.0349 AC XY: 2861AN XY: 81986
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0374 AC: 51399AN: 1373540Hom.: 109 AF XY: 0.0369 AC XY: 25129AN XY: 681136
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GnomAD4 genome AF: 0.0633 AC: 9020AN: 142440Hom.: 417 Cov.: 0 AF XY: 0.0628 AC XY: 4331AN XY: 69014
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 02, 2025 | - - |
Hypercholesterolemia, familial, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 05, 2017 | - - |
Familial hypercholesterolemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 04, 2017 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at