rs2239012

chr11-117217646-A-G

Variant summary

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

The NM_004716.4(PCSK7):c.1534+820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,072 control chromosomes in the GnomAD database, including 7,152 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 0.29 (7152 hom., cov: 32)
  • Exomes 𝑓: 0.28 (0 hom.)
• Consequence: PCSK7 NM_004716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

PCSK7 (HGNC:8748): (proprotein convertase subtilisin/kexin type 7) 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. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene has been implicated in the transcriptional regulation of housekeeping genes and plays a role in the regulation of iron metabolism. A t(11;14)(q23;q32) chromosome translocation associated with B-cell lymphoma occurs between this gene and its inverted counterpart. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK7	NM_004716.4	c.1534+820T>C		intron_variant		ENST00000320934.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK7	ENST00000320934.8	c.1534+820T>C		intron_variant		1	NM_004716.4	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43306 AN: 151936 Hom.: 7142 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.278 AC: 5 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 4 AN XY: 16

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.285 AC: 43342 AN: 152054 Hom.: 7152 Cov.: 32 AF XY: 0.285 AC XY: 21173 AN XY: 74326

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.252

Alfa AF: 0.260 Hom.: 884

Bravo AF: 0.297

Asia WGS AF: 0.236 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	6.9
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2239012; hg19: chr11-117088362;