rs494198
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_174936.4(PCSK9):c.799+64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,609,988 control chromosomes in the GnomAD database, including 333,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.61 ( 28677 hom., cov: 33)
Exomes 𝑓: 0.65 ( 304958 hom. )
Consequence
PCSK9
NM_174936.4 intron
NM_174936.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.373
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 1-55052855-C-A is Benign according to our data. Variant chr1-55052855-C-A is described in ClinVar as [Benign]. Clinvar id is 265935.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55052855-C-A is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK9 | NM_174936.4 | c.799+64C>A | intron_variant | ENST00000302118.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK9 | ENST00000302118.5 | c.799+64C>A | intron_variant | 1 | NM_174936.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.607 AC: 92182AN: 151892Hom.: 28665 Cov.: 33
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GnomAD4 exome AF: 0.645 AC: 940430AN: 1457978Hom.: 304958 AF XY: 0.643 AC XY: 465953AN XY: 725194
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GnomAD4 genome ? AF: 0.607 AC: 92240AN: 152010Hom.: 28677 Cov.: 33 AF XY: 0.603 AC XY: 44824AN XY: 74282
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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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at