dbSNP rs4674258: CXCR2:c.-140-428C>T (chr2-218125863-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000453237.5(CXCR2):c.-140-428C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,340 control chromosomes in the GnomAD database, including 19,169 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 0.50 ( 19101 hom., cov: 29)

Exomes 𝑓: 0.44 ( 68 hom. )

Consequence

CXCR2
ENST00000453237.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.496

Publications

15 publications found

Variant links:

Genes affected

CXCR2 (HGNC:6027): (C-X-C motif chemokine receptor 2) The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein activated second messenger system. This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. This receptor mediates neutrophil migration to sites of inflammation. The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. This gene, IL8RA, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. Alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2009]

CXCR2 Gene-Disease associations (from GenCC):

WHIM syndrome 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive severe congenital neutropenia due to CXCR2 deficiency
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

CXCR2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR2	NM_001557.4 link	c.-568C>T		upstream_gene_variant		ENST00000318507.7	NP_001548.1	P25025Q53PC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7 link	c.-568C>T		upstream_gene_variant		1	NM_001557.4	ENSP00000319635.2		P25025

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75493

AN:

151614

Hom.:

19080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.442

AC:

269

AN:

608

Hom.:

Cov.:

AF XY:

0.454

AC XY:

168

AN XY:

370

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.188

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.350

AC:

AN:

254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.540

AC:

150

AN:

278

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.498

AC:

75533

AN:

151732

Hom.:

19101

Cov.:

AF XY:

0.493

AC XY:

36581

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.543

AC:

22470

AN:

41356

American (AMR)

AF:

0.507

AC:

7725

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.574

AC:

1989

AN:

3464

East Asian (EAS)

AF:

0.327

AC:

1687

AN:

5152

South Asian (SAS)

AF:

0.494

AC:

2372

AN:

4802

European-Finnish (FIN)

AF:

0.399

AC:

4197

AN:

10532

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33146

AN:

67886

Other (OTH)

AF:

0.532

AC:

1120

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1860

3719

5579

7438

9298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.495

Hom.:

6961

Bravo

AF:

0.506

Asia WGS

AF:

0.392

AC:

1365

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.9

(source)

DANN

Benign

0.76

PhyloP100

0.50

PromoterAI

-0.0014

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs4674258

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over