11-117220893-G-C

Variant names:

• chr11-117220893-G-C
• rs236918
• NM_004716.4:c.1156-1135C>G

Variant summary

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

The NM_004716.4(PCSK7):​c.1156-1135C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,376 control chromosomes in the GnomAD database, including 2,366 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 0.15 (2360 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6 hom.)
• Consequence: PCSK7 NM_004716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358
• Publications: 59 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004716.4. 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.1156-1135C>G		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.1156-1135C>G		intron	N/A	ENSP00000325917.3
	PCSK7	ENST00000528217.1	TSL:4	n.2171C>G		non_coding_transcript_exon	Exon 1 of 3
	PCSK7	ENST00000524507.6	TSL:2	c.1156-1135C>G		intron	N/A	ENSP00000433841.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23308 AN: 152020 Hom.: 2346 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.168 AC: 40 AN: 238 Hom.: 6 Cov.: 0 AF XY: 0.172 AC XY: 31 AN XY: 180

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.625 AC: 5 AN: 8

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.144 AC: 30 AN: 208

Other (OTH) AF: 0.188 AC: 3 AN: 16

GnomAD4 genome AF: 0.153 AC: 23350 AN: 152138 Hom.: 2360 Cov.: 32 AF XY: 0.160 AC XY: 11878 AN XY: 74364

African (AFR) AF: 0.160 AC: 6635 AN: 41530

American (AMR) AF: 0.194 AC: 2970 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3466

East Asian (EAS) AF: 0.482 AC: 2484 AN: 5154

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4816

European-Finnish (FIN) AF: 0.136 AC: 1435 AN: 10580

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7253 AN: 67984

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.115 Hom.: 833

Bravo AF: 0.154

Asia WGS AF: 0.394 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		0.36
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: rs236918; hg19: chr11-117091609;