rs155971

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000311106.8(PCSK1):​c.709+1341A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,084 control chromosomes in the GnomAD database, including 26,008 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 0.57 ( 26008 hom., cov: 32)

Consequence

PCSK1
ENST00000311106.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.429
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCSK1NM_000439.5 linkuse as main transcriptc.709+1341A>G intron_variant ENST00000311106.8 NP_000430.3
LOC101929710NR_130776.1 linkuse as main transcriptn.354+35040T>C intron_variant, non_coding_transcript_variant
PCSK1NM_001177875.2 linkuse as main transcriptc.568+1341A>G intron_variant NP_001171346.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCSK1ENST00000311106.8 linkuse as main transcriptc.709+1341A>G intron_variant 1 NM_000439.5 ENSP00000308024 P1P29120-1
ENST00000502645.2 linkuse as main transcriptn.354+35040T>C intron_variant, non_coding_transcript_variant 5
PCSK1ENST00000508626.5 linkuse as main transcriptc.568+1341A>G intron_variant 2 ENSP00000421600 P29120-2

Frequencies

GnomAD3 genomes
AF:
0.574
AC:
87220
AN:
151966
Hom.:
26012
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.422
Gnomad AMI
AF:
0.588
Gnomad AMR
AF:
0.639
Gnomad ASJ
AF:
0.699
Gnomad EAS
AF:
0.537
Gnomad SAS
AF:
0.592
Gnomad FIN
AF:
0.502
Gnomad MID
AF:
0.627
Gnomad NFE
AF:
0.656
Gnomad OTH
AF:
0.622
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.574
AC:
87230
AN:
152084
Hom.:
26008
Cov.:
32
AF XY:
0.569
AC XY:
42307
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.421
Gnomad4 AMR
AF:
0.639
Gnomad4 ASJ
AF:
0.699
Gnomad4 EAS
AF:
0.537
Gnomad4 SAS
AF:
0.591
Gnomad4 FIN
AF:
0.502
Gnomad4 NFE
AF:
0.656
Gnomad4 OTH
AF:
0.624
Alfa
AF:
0.606
Hom.:
4806
Bravo
AF:
0.580
Asia WGS
AF:
0.522
AC:
1821
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
5.6
DANN
Benign
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs155971; hg19: chr5-95750396; API