rs516499

chr1-55061012-G-Achr1-55061012-G-Cchr1-55061012-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_174936.4(PCSK9):c.1682-363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,152 control chromosomes in the GnomAD database, including 52,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.83 (52277 hom., cov: 32)
• Consequence: PCSK9 NM_174936.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-55061012-G-A is Benign according to our data. Variant chr1-55061012-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK9	NM_174936.4	c.1682-363G>A		intron_variant		ENST00000302118.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK9	ENST00000302118.5	c.1682-363G>A		intron_variant		1	NM_174936.4	P2

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125831 AN: 152034 Hom.: 52247 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.854

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.828 AC: 125916 AN: 152152 Hom.: 52277 Cov.: 32 AF XY: 0.829 AC XY: 61640 AN XY: 74364

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.855

Alfa AF: 0.824 Hom.: 6935

Bravo AF: 0.831

Asia WGS AF: 0.921 AC: 3204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.80
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs516499; hg19: chr1-55526685; COSMIC: COSV56161344;