11-117204850-C-T

Variant names:

• chr11-117204850-C-T
• rs508487
• NM_004716.4:c.*1147G>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.*1147G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 267,740 control chromosomes in the GnomAD database, including 718 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 0.055 (321 hom., cov: 32)
  • Exomes 𝑓: 0.073 (397 hom.)
• Consequence: PCSK7 NM_004716.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 40 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]

TAGLN (HGNC:11553): (transgelin) This gene encodes a shape change and transformation sensitive actin-binding protein which belongs to the calponin family. It is ubiquitously expressed in vascular and visceral smooth muscle, and is an early marker of smooth muscle differentiation. The encoded protein is thought to be involved in calcium-independent smooth muscle contraction. It acts as a tumor suppressor, and the loss of its expression is an early event in cell transformation and the development of some tumors, coinciding with cellular plasticity. The encoded protein has a domain architecture consisting of an N-terminal calponin homology (CH) domain and a C-terminal calponin-like (CLIK) domain. Mice with a knockout of the orthologous gene are viable and fertile but their vascular smooth muscle cells exhibit alterations in the distribution of the actin filament and changes in cytoskeletal organization. [provided by RefSeq, Aug 2017]

ENSG00000280143 (HGNC:):

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 = 0.133 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK7	NM_004716.4	MANE Select	c.*1147G>A		3_prime_UTR	Exon 17 of 17	NP_004707.2
	TAGLN	NM_003186.5	MANE Select	c.*491C>T		3_prime_UTR	Exon 5 of 5	NP_003177.2
	TAGLN	NM_001001522.2		c.*491C>T		3_prime_UTR	Exon 5 of 5	NP_001001522.1	Q01995

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCSK7	ENST00000320934.8	TSL:1 MANE Select	c.*1147G>A		3_prime_UTR	Exon 17 of 17	ENSP00000325917.3	Q16549
	TAGLN	ENST00000392951.9	TSL:1 MANE Select	c.*491C>T		3_prime_UTR	Exon 5 of 5	ENSP00000376678.4	Q01995
	TAGLN	ENST00000278968.10	TSL:1	c.*491C>T		downstream_gene	N/A	ENSP00000278968.6	Q01995

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8305 AN: 151830 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0728 AC: 8432 AN: 115814 Hom.: 397 Cov.: 0 AF XY: 0.0762 AC XY: 4508 AN XY: 59154

African (AFR) AF: 0.00910 AC: 38 AN: 4174

American (AMR) AF: 0.0588 AC: 338 AN: 5750

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 336 AN: 3776

East Asian (EAS) AF: 0.118 AC: 1180 AN: 9974

South Asian (SAS) AF: 0.123 AC: 1701 AN: 13786

European-Finnish (FIN) AF: 0.0705 AC: 305 AN: 4328

Middle Eastern (MID) AF: 0.0785 AC: 38 AN: 484

European-Non Finnish (NFE) AF: 0.0608 AC: 4065 AN: 66884

Other (OTH) AF: 0.0647 AC: 431 AN: 6658

GnomAD4 genome AF: 0.0547 AC: 8311 AN: 151926 Hom.: 321 Cov.: 32 AF XY: 0.0566 AC XY: 4200 AN XY: 74220

African (AFR) AF: 0.0131 AC: 541 AN: 41428

American (AMR) AF: 0.0703 AC: 1071 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3468

East Asian (EAS) AF: 0.141 AC: 731 AN: 5168

South Asian (SAS) AF: 0.123 AC: 589 AN: 4802

European-Finnish (FIN) AF: 0.0594 AC: 624 AN: 10512

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0631 AC: 4291 AN: 67994

Other (OTH) AF: 0.0636 AC: 134 AN: 2108

Alfa AF: 0.0595 Hom.: 1104

Bravo AF: 0.0510

Asia WGS AF: 0.116 AC: 401 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	3.3
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: rs508487; hg19: chr11-117075566;