4-73740676-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000584.4(CXCL8):c.18C>T(p.Ala6Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,578 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 4 hom. )

Consequence

CXCL8
NM_000584.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.25

Publications

7 publications found

Variant links:

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]

CXCL8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 4-73740676-C-T is Benign according to our data. Variant chr4-73740676-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 708667.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.25 with no splicing effect.

BS2

High AC in GnomAd4 at 199 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000584.4. 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
	CXCL8	NM_000584.4	MANE Select	c.18C>T	p.Ala6Ala	synonymous	Exon 1 of 4	NP_000575.1
	CXCL8	NM_001354840.3		c.18C>T	p.Ala6Ala	synonymous	Exon 1 of 3	NP_001341769.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CXCL8	ENST00000307407.8	TSL:1 MANE Select	c.18C>T	p.Ala6Ala	synonymous	Exon 1 of 4	ENSP00000306512.3
CXCL8	ENST00000401931.2	TSL:1	c.18C>T	p.Ala6Ala	synonymous	Exon 1 of 3	ENSP00000385908.1
CXCL8	ENST00000483500.1	TSL:2	n.108C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

199

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00126

AC:

316

AN:

250850

AF XY:

0.00130

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.000726

Gnomad ASJ exome

AF:

0.00596

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00160

AC:

2335

AN:

1461310

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1195

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33412

American (AMR)

AF:

0.000783

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00616

AC:

161

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.000626

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00176

AC:

1955

AN:

1111646

Other (OTH)

AF:

0.00179

AC:

108

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

118

236

355

473

591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00131

AC:

199

AN:

152268

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41560

American (AMR)

AF:

0.000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00104

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00198

AC:

135

AN:

68022

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00137

EpiCase

AF:

0.00120

EpiControl

AF:

0.00173

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.99

(source)

DANN

Benign

0.76

PhyloP100

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over