11-117219842-C-T

Variant names:

• chr11-117219842-C-T
• rs74830
• NM_004716.4:c.1156-84G>A

Variant summary

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

The ENST00000320934.8(PCSK7):​c.1156-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,053,096 control chromosomes in the GnomAD database, including 113,225 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 (24375 hom., cov: 33)
  • Exomes 𝑓: 0.43 (88850 hom.)
• Consequence: PCSK7 ENST00000320934.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000320934.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK7	NM_004716.4	MANE Select	c.1156-84G>A		intron	N/A	NP_004707.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK7	ENST00000320934.8	TSL:1 MANE Select	c.1156-84G>A		intron	N/A	ENSP00000325917.3
	PCSK7	ENST00000527037.5	TSL:3	n.297G>A		non_coding_transcript_exon	Exon 1 of 6
	PCSK7	ENST00000524507.6	TSL:2	c.1156-84G>A		intron	N/A	ENSP00000433841.2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81665 AN: 152048 Hom.: 24318 Cov.: 33

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.499

GnomAD4 exome AF: 0.430 AC: 387369 AN: 900930 Hom.: 88850 Cov.: 11 AF XY: 0.437 AC XY: 196725 AN XY: 450684

African (AFR) AF: 0.794 AC: 14929 AN: 18812

American (AMR) AF: 0.590 AC: 10258 AN: 17378

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 7867 AN: 16068

East Asian (EAS) AF: 0.680 AC: 19998 AN: 29412

South Asian (SAS) AF: 0.704 AC: 34689 AN: 49248

European-Finnish (FIN) AF: 0.477 AC: 22441 AN: 47058

Middle Eastern (MID) AF: 0.539 AC: 2239 AN: 4156

European-Non Finnish (NFE) AF: 0.378 AC: 256436 AN: 678582

Other (OTH) AF: 0.460 AC: 18512 AN: 40216

GnomAD4 genome AF: 0.537 AC: 81781 AN: 152166 Hom.: 24375 Cov.: 33 AF XY: 0.545 AC XY: 40563 AN XY: 74402

African (AFR) AF: 0.778 AC: 32304 AN: 41518

American (AMR) AF: 0.531 AC: 8120 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3515 AN: 5178

South Asian (SAS) AF: 0.720 AC: 3471 AN: 4822

European-Finnish (FIN) AF: 0.488 AC: 5167 AN: 10584

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

European-Non Finnish (NFE) AF: 0.385 AC: 26155 AN: 67982

Other (OTH) AF: 0.504 AC: 1060 AN: 2104

Alfa AF: 0.487 Hom.: 2589

Bravo AF: 0.549

Asia WGS AF: 0.718 AC: 2497 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.27
PhyloP100		-0.16
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: rs74830; hg19: chr11-117090558; COSMIC: COSV58006367; COSMIC: COSV58006367;