chr11-117224645-C-T

Variant names:

• chr11-117224645-C-T
• rs236919
• NM_004716.4:c.915+56G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004716.4(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 NM_004716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCSK7	NM_004716.4	c.915+56G>A		intron_variant	Intron 7 of 16	ENST00000320934.8	NP_004707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK7	ENST00000320934.8	c.915+56G>A		intron_variant	Intron 7 of 16	1	NM_004716.4	ENSP00000325917.3

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

African (AFR) AF: 0.816 AC: 23783 AN: 29154

American (AMR) AF: 0.602 AC: 26762 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 12326 AN: 24664

East Asian (EAS) AF: 0.673 AC: 25991 AN: 38614

South Asian (SAS) AF: 0.691 AC: 56443 AN: 81742

European-Finnish (FIN) AF: 0.477 AC: 25451 AN: 53330

Middle Eastern (MID) AF: 0.533 AC: 2828 AN: 5310

European-Non Finnish (NFE) AF: 0.375 AC: 337318 AN: 898648

Other (OTH) AF: 0.466 AC: 24500 AN: 52616

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

African (AFR) AF: 0.802 AC: 33263 AN: 41486

American (AMR) AF: 0.534 AC: 8143 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3498 AN: 5178

South Asian (SAS) AF: 0.705 AC: 3403 AN: 4828

European-Finnish (FIN) AF: 0.489 AC: 5156 AN: 10548

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26105 AN: 67940

Other (OTH) AF: 0.511 AC: 1079 AN: 2110

Alfa AF: 0.438 Hom.: 66574

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
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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