1-55058666-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGT

Position:

• chr1-55058666-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000302118.5(PCSK9):​c.1503+52_1503+71del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00093 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCSK9 ENST00000302118.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.564

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 1-55058666-CGTGTGTGTGTGTGTGTGTGT-C is Benign according to our data. Variant chr1-55058666-CGTGTGTGTGTGTGTGTGTGT-C is described in ClinVar as [Benign]. Clinvar id is 492234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-55058666-CGTGTGTGTGTGTGTGTGTGT-C is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCSK9	NM_174936.4	c.1503+52_1503+71del		intron_variant		ENST00000302118.5	NP_777596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCSK9	ENST00000302118.5	c.1503+52_1503+71del		intron_variant		1	NM_174936.4	ENSP00000303208	P2

Frequencies

GnomAD3 genomes AF: 0.000498 AC: 71 AN: 142430 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000685

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000421

Gnomad SAS AF: 0.000457

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000612

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000929 AC: 1293 AN: 1391270 Hom.: 1 AF XY: 0.000918 AC XY: 633 AN XY: 689848

Gnomad4 AFR exome AF: 0.00710

Gnomad4 AMR exome AF: 0.000531

Gnomad4 ASJ exome AF: 0.00169

Gnomad4 EAS exome AF: 0.00108

Gnomad4 SAS exome AF: 0.000837

Gnomad4 FIN exome AF: 0.00148

Gnomad4 NFE exome AF: 0.000714

Gnomad4 OTH exome AF: 0.000974

GnomAD4 genome AF: 0.000498 AC: 71 AN: 142510 Hom.: 0 Cov.: 0 AF XY: 0.000492 AC XY: 34 AN XY: 69046

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.0000685

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000422

Gnomad4 SAS AF: 0.000457

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000613

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypercholesterolemia, autosomal dominant, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 07, 2024

- -

Hypercholesterolemia, familial, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Sep 05, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35115360; hg19: chr1-55524339;