1-55058666-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_174936.4(PCSK9):​c.1503+62_1503+71delGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 27 hom., cov: 0)
Exomes 𝑓: 0.0021 ( 7 hom. )
Failed GnomAD Quality Control

Consequence

PCSK9
NM_174936.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 -10 ACMG points.

BP6
Variant 1-55058666-CGTGTGTGTGT-C is Benign according to our data. Variant chr1-55058666-CGTGTGTGTGT-C is described in ClinVar as [Benign]. Clinvar id is 1598662.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-55058666-CGTGTGTGTGT-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00843 (1201/142496) while in subpopulation AFR AF= 0.0258 (977/37854). AF 95% confidence interval is 0.0245. There are 27 homozygotes in gnomad4. There are 538 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1201 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCSK9NM_174936.4 linkc.1503+62_1503+71delGTGTGTGTGT 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+29delGTGTGTGTGT intron_variant 1 NM_174936.4 ENSP00000303208.5 Q8NBP7-1

Frequencies

GnomAD3 genomes
AF:
0.00838
AC:
1194
AN:
142416
Hom.:
27
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0257
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00446
Gnomad ASJ
AF:
0.00238
Gnomad EAS
AF:
0.00400
Gnomad SAS
AF:
0.00320
Gnomad FIN
AF:
0.000328
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00159
Gnomad OTH
AF:
0.00566
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00206
AC:
2864
AN:
1392040
Hom.:
7
AF XY:
0.00197
AC XY:
1359
AN XY:
690178
show subpopulations
Gnomad4 AFR exome
AF:
0.0246
Gnomad4 AMR exome
AF:
0.00405
Gnomad4 ASJ exome
AF:
0.00169
Gnomad4 EAS exome
AF:
0.00287
Gnomad4 SAS exome
AF:
0.00182
Gnomad4 FIN exome
AF:
0.000855
Gnomad4 NFE exome
AF:
0.00128
Gnomad4 OTH exome
AF:
0.00363
GnomAD4 genome
AF:
0.00843
AC:
1201
AN:
142496
Hom.:
27
Cov.:
0
AF XY:
0.00779
AC XY:
538
AN XY:
69036
show subpopulations
Gnomad4 AFR
AF:
0.0258
Gnomad4 AMR
AF:
0.00445
Gnomad4 ASJ
AF:
0.00238
Gnomad4 EAS
AF:
0.00401
Gnomad4 SAS
AF:
0.00320
Gnomad4 FIN
AF:
0.000328
Gnomad4 NFE
AF:
0.00159
Gnomad4 OTH
AF:
0.00562

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hypercholesterolemia, autosomal dominant, 3 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 02, 2025- -

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