11-117218278-A-G

Position:

• chr11-117218278-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+188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 262,352 control chromosomes in the GnomAD database, including 9,953 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 0.28 (6561 hom., cov: 31)
  • Exomes 𝑓: 0.26 (3392 hom.)
• Consequence: PCSK7 NM_004716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK7	NM_004716.4	c.1534+188T>C		intron_variant		ENST00000320934.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK7	ENST00000320934.8	c.1534+188T>C		intron_variant		1	NM_004716.4	P1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 41976 AN: 150966 Hom.: 6554 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.256 AC: 28497 AN: 111260 Hom.: 3392 Cov.: 3 AF XY: 0.255 AC XY: 15279 AN XY: 59892

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.313

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.278 AC: 42010 AN: 151092 Hom.: 6561 Cov.: 31 AF XY: 0.278 AC XY: 20529 AN XY: 73810

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.245

Alfa AF: 0.218 Hom.: 6500

Bravo AF: 0.288

Asia WGS AF: 0.235 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.82

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: rs2239011; hg19: chr11-117088994;