chr4-73741568-G-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2
The NM_000584.4(CXCL8):c.91G>T(p.Glu31Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000943 in 1,613,502 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00090 ( 3 hom. )
Consequence
CXCL8
NM_000584.4 stop_gained
NM_000584.4 stop_gained
Scores
4
1
2
Clinical Significance
Conservation
PhyloP100: 5.57
Genes affected
CXCL8 (HGNC:6025): (C-X-C motif chemokine ligand 8) The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is commonly referred to as interleukin-8 (IL-8). IL-8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection. Bacterial and viral products rapidly induce IL-8 expression. IL-8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). This gene is believed to play a role in the pathogenesis of the lower respiratory tract infection bronchiolitis, a common respiratory tract disease caused by the respiratory syncytial virus (RSV). The overproduction of this proinflammatory protein is thought to cause the lung inflammation associated with csytic fibrosis. This proinflammatory protein is also suspected of playing a role in coronary artery disease and endothelial dysfunction. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor. The binding of IL-8 to one of its receptors (IL-8RB/CXCR2) increases the permeability of blood vessels and increasing levels of IL-8 are positively correlated with increased severity of multiple disease outcomes (eg, sepsis). This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM4
?
Stoplost variant in NM_000584.4 Downstream stopcodon found after 129 codons.
BP6
?
Variant 4-73741568-G-T is Benign according to our data. Variant chr4-73741568-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038842.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 206 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CXCL8 | NM_000584.4 | c.91G>T | p.Glu31Ter | stop_gained | 2/4 | ENST00000307407.8 | |
CXCL8 | NM_001354840.3 | c.91G>T | p.Glu31Ter | stop_gained | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CXCL8 | ENST00000307407.8 | c.91G>T | p.Glu31Ter | stop_gained | 2/4 | 1 | NM_000584.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00135 AC: 206AN: 152104Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00135 AC: 338AN: 250748Hom.: 1 AF XY: 0.00132 AC XY: 179AN XY: 135550
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GnomAD4 exome AF: 0.000900 AC: 1315AN: 1461280Hom.: 3 Cov.: 31 AF XY: 0.000942 AC XY: 685AN XY: 726972
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GnomAD4 genome ? AF: 0.00135 AC: 206AN: 152222Hom.: 1 Cov.: 33 AF XY: 0.00155 AC XY: 115AN XY: 74430
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CXCL8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 31, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at