dbSNP rs17844765: CXCR2:c.*355C>A (chr2-218136239-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001557.4(CXCR2):c.*355C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CXCR2
NM_001557.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.789

Publications

0 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:

ENSG00000305582 (HGNC:):

ENSG00000305582 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR2	NM_001557.4 link	c.*355C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000318507.7	NP_001548.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CXCR2	ENST00000318507.7 link	c.*355C>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_001557.4	ENSP00000319635.2
ENSG00000305582	ENST00000811769.1 link	n.152+3651G>T	intron_variant	Intron 2 of 2
ENSG00000305582	ENST00000811770.1 link	n.208+3651G>T	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147644

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

51782

Hom.:

Cov.:

AF XY:

0.0000389

AC XY:

AN XY:

25720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1306

American (AMR)

AF:

0.000459

AC:

AN:

2180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1392

East Asian (EAS)

AF:

0.00

AC:

AN:

2586

South Asian (SAS)

AF:

0.00

AC:

AN:

1212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

24544

Other (OTH)

AF:

0.00

AC:

AN:

2434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

147644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71698

African (AFR)

AF:

0.00

AC:

AN:

39598

American (AMR)

AF:

0.00

AC:

AN:

14556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67256

Other (OTH)

AF:

0.00

AC:

AN:

2022

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.61

(source)

DANN

Benign

0.37

PhyloP100

-0.79

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over