dbSNP rs13306441: CXCR2:c.*338A>G (chr2-218136222-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001557.4(CXCR2):c.*338A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 225,106 control chromosomes in the GnomAD database, including 97 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 0.025 ( 56 hom., cov: 30)

Exomes 𝑓: 0.026 ( 41 hom. )

Consequence

CXCR2
NM_001557.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.377

Publications

2 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0246 (3743/152010) while in subpopulation SAS AF = 0.0479 (230/4798). AF 95% confidence interval is 0.0429. There are 56 homozygotes in GnomAd4. There are 1878 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR2	NM_001557.4 link	c.*338A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000318507.7	NP_001548.1	P25025Q53PC4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CXCR2	ENST00000318507.7 link	c.*338A>G	3_prime_UTR_variant	Exon 3 of 3	1	NM_001557.4	ENSP00000319635.2	P25025
ENSG00000305582	ENST00000811769.1 link	n.152+3668T>C	intron_variant	Intron 2 of 2
ENSG00000305582	ENST00000811770.1 link	n.208+3668T>C	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3741

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00620

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.0481

Gnomad FIN

AF:

0.0260

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0317

Gnomad OTH

AF:

0.0332

GnomAD4 exome

AF:

0.0262

AC:

1918

AN:

73096

Hom.:

Cov.:

AF XY:

0.0272

AC XY:

996

AN XY:

36642

show subpopulations

African (AFR)

AF:

0.00580

AC:

AN:

2070

American (AMR)

AF:

0.0222

AC:

AN:

3150

Ashkenazi Jewish (ASJ)

AF:

0.0514

AC:

115

AN:

2236

East Asian (EAS)

AF:

0.0118

AC:

AN:

4392

South Asian (SAS)

AF:

0.0452

AC:

AN:

1724

European-Finnish (FIN)

AF:

0.0203

AC:

349

AN:

17192

Middle Eastern (MID)

AF:

0.0639

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0291

AC:

1112

AN:

38166

Other (OTH)

AF:

0.0290

AC:

113

AN:

3900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

194

292

389

486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0246

AC:

3743

AN:

152010

Hom.:

Cov.:

AF XY:

0.0253

AC XY:

1878

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.00620

AC:

257

AN:

41444

American (AMR)

AF:

0.0219

AC:

334

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

243

AN:

3470

East Asian (EAS)

AF:

0.0257

AC:

133

AN:

5178

South Asian (SAS)

AF:

0.0479

AC:

230

AN:

4798

European-Finnish (FIN)

AF:

0.0260

AC:

276

AN:

10602

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0317

AC:

2158

AN:

67976

Other (OTH)

AF:

0.0329

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

187

373

560

746

933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0315

Hom.:

114

Bravo

AF:

0.0226

Asia WGS

AF:

0.0550

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.40

PhyloP100

0.38

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

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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