rs271924
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000439.5(PCSK1):c.1197-1534T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,880 control chromosomes in the GnomAD database, including 8,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.33 ( 8448 hom., cov: 31)
Consequence
PCSK1
NM_000439.5 intron
NM_000439.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.22
Genes affected
PCSK1 (HGNC:8743): (proprotein convertase subtilisin/kexin type 1) 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 initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK1 | NM_000439.5 | c.1197-1534T>A | intron_variant | ENST00000311106.8 | |||
LOC101929710 | NR_130776.1 | n.354+22068A>T | intron_variant, non_coding_transcript_variant | ||||
PCSK1 | NM_001177875.2 | c.1056-1534T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK1 | ENST00000311106.8 | c.1197-1534T>A | intron_variant | 1 | NM_000439.5 | P1 | |||
ENST00000502645.2 | n.354+22068A>T | intron_variant, non_coding_transcript_variant | 5 | ||||||
PCSK1 | ENST00000513085.1 | n.340-1534T>A | intron_variant, non_coding_transcript_variant | 1 | |||||
PCSK1 | ENST00000508626.5 | c.1056-1534T>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.325 AC: 49366AN: 151760Hom.: 8443 Cov.: 31
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.325 AC: 49382AN: 151880Hom.: 8448 Cov.: 31 AF XY: 0.322 AC XY: 23930AN XY: 74216
GnomAD4 genome
?
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23930
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942
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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