11-117218278-A-G

Variant names:

• chr11-117218278-A-G
• rs2239011
• NM_004716.4:c.1534+188T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 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.1534+188T>C		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.1534+188T>C		intron	N/A	ENSP00000325917.3
	PCSK7	ENST00000528973.1	TSL:3	n.187T>C		non_coding_transcript_exon	Exon 1 of 2
	PCSK7	ENST00000524507.6	TSL:2	c.1534+188T>C		intron	N/A	ENSP00000433841.2

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

African (AFR) AF: 0.481 AC: 1368 AN: 2842

American (AMR) AF: 0.324 AC: 989 AN: 3054

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1132 AN: 3622

East Asian (EAS) AF: 0.243 AC: 1950 AN: 8018

South Asian (SAS) AF: 0.258 AC: 2720 AN: 10552

European-Finnish (FIN) AF: 0.299 AC: 2688 AN: 9004

Middle Eastern (MID) AF: 0.253 AC: 120 AN: 474

European-Non Finnish (NFE) AF: 0.235 AC: 15847 AN: 67304

Other (OTH) AF: 0.263 AC: 1683 AN: 6390

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

African (AFR) AF: 0.426 AC: 17572 AN: 41294

American (AMR) AF: 0.256 AC: 3898 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 941 AN: 3450

East Asian (EAS) AF: 0.162 AC: 818 AN: 5042

South Asian (SAS) AF: 0.265 AC: 1256 AN: 4736

European-Finnish (FIN) AF: 0.271 AC: 2800 AN: 10332

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 13991 AN: 67740

Other (OTH) AF: 0.245 AC: 514 AN: 2094

Alfa AF: 0.232 Hom.: 12002

Bravo AF: 0.288

Asia WGS AF: 0.235 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		0.65
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: rs2239011; hg19: chr11-117088994;