rs2227306

Variant names:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong

The NM_000584.4(CXCL8):c.65-204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.315 (AC=47,926) in the gnomAD database across 152,034 control chromosomes, including 8,700 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.416. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8700 hom., cov: 32)

Consequence

CXCL8
NM_000584.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

Publications

192 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:

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new If you want to explore the variant's impact on the transcript NM_000584.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4157 — exceeds 5%% threshold (BA1 applied)

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL8	NM_000584.4	MANE Select	c.65-204C>T		intron	N/A	NP_000575.1	P10145
	CXCL8	NM_001354840.3		c.65-204C>T		intron	N/A	NP_001341769.1	C9J4T6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CXCL8	ENST00000307407.8	TSL:1 MANE Select	c.65-204C>T	intron	N/A	ENSP00000306512.3	P10145
CXCL8	ENST00000401931.2	TSL:1	c.65-204C>T	intron	N/A	ENSP00000385908.1	C9J4T6
CXCL8	ENST00000483500.1	TSL:2	n.155-204C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47926

AN:

151916

Hom.:

8704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.315

AC:

47926

AN:

152034

Hom.:

8700

Cov.:

AF XY:

0.310

AC XY:

23047

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.133

AC:

5499

AN:

41482

American (AMR)

AF:

0.297

AC:

4536

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1207

AN:

3472

East Asian (EAS)

AF:

0.330

AC:

1706

AN:

5168

South Asian (SAS)

AF:

0.278

AC:

1337

AN:

4816

European-Finnish (FIN)

AF:

0.373

AC:

3936

AN:

10566

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.420

AC:

28527

AN:

67960

Other (OTH)

AF:

0.340

AC:

716

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1585

3170

4755

6340

7925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.354

Hom.:

1691

Bravo

AF:

0.306

Asia WGS

AF:

0.276

AC:

961

AN:

3478

Local populations

Turkish Variome

AF:

0.356

AC:

550

AN:

1546

Hom.:

108

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.369

AC:

3303

AN:

8960

Hom.:

620

ABraOM SABE-WGS-1171

AF:

0.318

AC:

745

AN:

2342

Hom.:

125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.45

(source)

DANN

Benign

0.37

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over