chr11-117224645-C-T

Position:

• chr11-117224645-C-T

Variant summary

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

The ENST00000320934.8(PCSK7):​c.915+56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,380,538 control chromosomes in the GnomAD database, including 151,366 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 0.54 (25081 hom., cov: 32)
  • Exomes 𝑓: 0.44 (126285 hom.)
• Consequence: PCSK7 ENST00000320934.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCSK7	NM_004716.4	c.915+56G>A		intron_variant		ENST00000320934.8	NP_004707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCSK7	ENST00000320934.8	c.915+56G>A		intron_variant		1	NM_004716.4	ENSP00000325917	P1
PCSK7	ENST00000524507.6	c.915+56G>A		intron_variant		2		ENSP00000433841	P1
PCSK7	ENST00000676339.1	c.915+56G>A		intron_variant				ENSP00000501995	P1
PCSK7	ENST00000534529.5	n.2176+56G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82541 AN: 151904 Hom.: 25014 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.506

GnomAD4 exome AF: 0.436 AC: 535402 AN: 1228516 Hom.: 126285 AF XY: 0.443 AC XY: 275558 AN XY: 622532

Gnomad4 AFR exome AF: 0.816

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.673

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.544 AC: 82667 AN: 152022 Hom.: 25081 Cov.: 32 AF XY: 0.551 AC XY: 40995 AN XY: 74338

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.511

Alfa AF: 0.419 Hom.: 28962

Bravo AF: 0.557

Asia WGS AF: 0.714 AC: 2484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.20
DANN	Benign	0.63

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: rs236919; hg19: chr11-117095361; COSMIC: COSV58006376; COSMIC: COSV58006376;