rs9326034

Variant names:

• chr1-55064991-G-A
• rs9326034
• NM_174936.4:c.*1407G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-55064991-G-A
• chr1-55064991-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174936.4(PCSK9):​c.*1407G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,224 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.023 (101 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCSK9 NM_174936.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK9	NM_174936.4	c.*1407G>A		downstream_gene_variant		ENST00000302118.5	NP_777596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK9	ENST00000302118.5	c.*1407G>A		downstream_gene_variant		1	NM_174936.4	ENSP00000303208.5

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3464 AN: 152106 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00757

Gnomad OTH AF: 0.0129

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0228 AC: 3472 AN: 152224 Hom.: 101 Cov.: 32 AF XY: 0.0223 AC XY: 1663 AN XY: 74426

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.00757

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0112 Hom.: 4

Bravo AF: 0.0236

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9326034; hg19: chr1-55530664;