Variant 1-55058666-CGTGTGTGTGT-C details in Genebe, Genetics Data Aggregator

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]

PCSK9 links:

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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
PCSK9	NM_174936.4 link	c.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
PCSK9	ENST00000302118.5 link	c.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.:

Cov.:

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.:

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.:

Cov.:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 02, 2025

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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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over