GeneBe

rs35115360

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_174936.4(PCSK9):​c.1503+36_1503+71delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,535,352 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 0)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

PCSK9
NM_174936.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.564

Publications

1 publications found
Variant links:
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, 3
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • homozygous familial hypercholesterolemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174936.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PCSK9
NM_174936.4
MANE Select
c.1503+36_1503+71delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT
intron
N/ANP_777596.2
PCSK9
NM_001407240.1
c.1626+36_1626+71delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT
intron
N/ANP_001394169.1A0AAQ5BGX4
PCSK9
NM_001407241.1
c.1503+36_1503+71delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT
intron
N/ANP_001394170.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PCSK9
ENST00000302118.5
TSL:1 MANE Select
c.1503+20_1503+55delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT
intron
N/AENSP00000303208.5Q8NBP7-1
PCSK9
ENST00000710286.1
c.1860+20_1860+55delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT
intron
N/AENSP00000518176.1A0AA34QVH0
PCSK9
ENST00000713786.1
c.1626+20_1626+55delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT
intron
N/AENSP00000519088.1A0AAQ5BGX4

Frequencies

GnomAD3 genomes
AF:
0.00000702
AC:
1
AN:
142440
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000153
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.18e-7
AC:
1
AN:
1392912
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
690658
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31628
American (AMR)
AF:
0.00
AC:
0
AN:
39552
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24880
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36988
South Asian (SAS)
AF:
0.0000123
AC:
1
AN:
81354
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47988
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4014
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1068944
Other (OTH)
AF:
0.00
AC:
0
AN:
57564
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000702
AC:
1
AN:
142440
Hom.:
0
Cov.:
0
AF XY:
0.0000145
AC XY:
1
AN XY:
68950
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
37766
American (AMR)
AF:
0.00
AC:
0
AN:
14588
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3364
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4752
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4378
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9152
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
296
European-Non Finnish (NFE)
AF:
0.0000153
AC:
1
AN:
65320
Other (OTH)
AF:
0.00
AC:
0
AN:
1944
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs35115360; hg19: chr1-55524339; API