chr1-55058666-CGTGTGTGTGTGTGTGTGT-C

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.564
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]

Genome browser will be placed here

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

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCSK9NM_174936.4 linkc.1503+54_1503+71delGTGTGTGTGTGTGTGTGT intron_variant ENST00000302118.5 NP_777596.2 Q8NBP7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCSK9ENST00000302118.5 linkc.1503+20_1503+37delGTGTGTGTGTGTGTGTGT intron_variant 1 NM_174936.4 ENSP00000303208.5 Q8NBP7-1

Frequencies

GnomAD3 genomes
AF:
0.0633
AC:
9006
AN:
142358
Hom.:
418
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.130
Gnomad AMI
AF:
0.0511
Gnomad AMR
AF:
0.0290
Gnomad ASJ
AF:
0.0544
Gnomad EAS
AF:
0.0467
Gnomad SAS
AF:
0.0281
Gnomad FIN
AF:
0.0483
Gnomad MID
AF:
0.0442
Gnomad NFE
AF:
0.0396
Gnomad OTH
AF:
0.0433
GnomAD3 exomes
AF:
0.0361
AC:
5378
AN:
149146
Hom.:
141
AF XY:
0.0349
AC XY:
2861
AN XY:
81986
show subpopulations
Gnomad AFR exome
AF:
0.0977
Gnomad AMR exome
AF:
0.0216
Gnomad ASJ exome
AF:
0.0543
Gnomad EAS exome
AF:
0.0443
Gnomad SAS exome
AF:
0.0280
Gnomad FIN exome
AF:
0.0443
Gnomad NFE exome
AF:
0.0308
Gnomad OTH exome
AF:
0.0361
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0374
AC:
51399
AN:
1373540
Hom.:
109
AF XY:
0.0369
AC XY:
25129
AN XY:
681136
show subpopulations
Gnomad4 AFR exome
AF:
0.122
Gnomad4 AMR exome
AF:
0.0222
Gnomad4 ASJ exome
AF:
0.0519
Gnomad4 EAS exome
AF:
0.0463
Gnomad4 SAS exome
AF:
0.0267
Gnomad4 FIN exome
AF:
0.0441
Gnomad4 NFE exome
AF:
0.0351
Gnomad4 OTH exome
AF:
0.0414
GnomAD4 genome
AF:
0.0633
AC:
9020
AN:
142440
Hom.:
417
Cov.:
0
AF XY:
0.0628
AC XY:
4331
AN XY:
69014
show subpopulations
Gnomad4 AFR
AF:
0.130
Gnomad4 AMR
AF:
0.0289
Gnomad4 ASJ
AF:
0.0544
Gnomad4 EAS
AF:
0.0460
Gnomad4 SAS
AF:
0.0286
Gnomad4 FIN
AF:
0.0483
Gnomad4 NFE
AF:
0.0396
Gnomad4 OTH
AF:
0.0430

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 02, 2025- -
Hypercholesterolemia, familial, 1 Benign:1
Likely benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthAug 05, 2017- -
Familial hypercholesterolemia Benign:1
Benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthDec 04, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs35115360; hg19: chr1-55524339; API