1-55058666-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Position:

• chr1-55058666-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000302118.5(PCSK9):​c.1503+66_1503+71dup 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 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: PCSK9 ENST00000302118.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-55058666-C-CGTGTGT is Benign according to our data. Variant chr1-55058666-C-CGTGTGT is described in ClinVar as [Likely_benign]. Clinvar id is 1660177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 220 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCSK9	NM_174936.4	c.1503+66_1503+71dup		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+66_1503+71dup		intron_variant		1	NM_174936.4	ENSP00000303208	P2

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 220 AN: 142424 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000411

Gnomad ASJ AF: 0.00297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000228

Gnomad FIN AF: 0.00394

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00217

Gnomad OTH AF: 0.000514

GnomAD4 exome AF: 0.000649 AC: 904 AN: 1391992 Hom.: 0 Cov.: 0 AF XY: 0.000684 AC XY: 472 AN XY: 690208

Gnomad4 AFR exome AF: 0.000285

Gnomad4 AMR exome AF: 0.000228

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.0000270

Gnomad4 SAS exome AF: 0.000664

Gnomad4 FIN exome AF: 0.00186

Gnomad4 NFE exome AF: 0.000631

Gnomad4 OTH exome AF: 0.000626

GnomAD4 genome AF: 0.00154 AC: 220 AN: 142504 Hom.: 0 Cov.: 0 AF XY: 0.00162 AC XY: 112 AN XY: 69040

Gnomad4 AFR AF: 0.000634

Gnomad4 AMR AF: 0.000411

Gnomad4 ASJ AF: 0.00297

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000229

Gnomad4 FIN AF: 0.00394

Gnomad4 NFE AF: 0.00217

Gnomad4 OTH AF: 0.000511

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypercholesterolemia, autosomal dominant, 3 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

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;