Variant chr1-55058666-CGTGTGTGTGTGTGTGTGT-C details in Genebe, Genetics Data Aggregator

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]

PCSK9 links:

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

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.:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 02, 2025

- -

Hypercholesterolemia, familial, 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Aug 05, 2017

- -

Familial hypercholesterolemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Dec 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.

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