rs7552841

chr1-55053079-C-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.799+288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,954 control chromosomes in the GnomAD database, including 8,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.32 (8317 hom., cov: 31)
• Consequence: PCSK9 NM_174936.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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=-0.92).
• BP6: Variant 1-55053079-C-T is Benign according to our data. Variant chr1-55053079-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK9	NM_174936.4	c.799+288C>T		intron_variant		ENST00000302118.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK9	ENST00000302118.5	c.799+288C>T		intron_variant		1	NM_174936.4	P2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48764 AN: 151834 Hom.: 8317 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.321 AC: 48770 AN: 151954 Hom.: 8317 Cov.: 31 AF XY: 0.318 AC XY: 23628 AN XY: 74268

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.359

Alfa AF: 0.352 Hom.: 2595

Bravo AF: 0.316

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.4
Dann	Benign	0.61

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: rs7552841; hg19: chr1-55518752;