rs1126579

Variant names:

• chr2-218136011-T-C
• rs1126579
• NM_001557.4:c.*127T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001557.4(CXCR2):​c.*127T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,294,684 control chromosomes in the GnomAD database, including 197,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (30342 hom., cov: 30)
  • Exomes 𝑓: 0.54 (167110 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.752
• Publications: 80 publications found

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: Ambry Genetics, Orphanet

ENSG00000305582 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-218136011-T-C is Benign according to our data. Variant chr2-218136011-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001557.4. 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
	CXCR2	NM_001557.4	MANE Select	c.*127T>C		3_prime_UTR	Exon 3 of 3	NP_001548.1	P25025
	CXCR2	NM_001168298.2		c.*127T>C		3_prime_UTR	Exon 4 of 4	NP_001161770.1	P25025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR2	ENST00000318507.7	TSL:1 MANE Select	c.*127T>C		3_prime_UTR	Exon 3 of 3	ENSP00000319635.2	P25025
	CXCR2	ENST00000875238.1		c.*127T>C		3_prime_UTR	Exon 3 of 3	ENSP00000545297.1
	CXCR2	ENST00000875239.1		c.*127T>C		3_prime_UTR	Exon 3 of 3	ENSP00000545298.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93167 AN: 151812 Hom.: 30290 Cov.: 30

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.537 AC: 614201 AN: 1142754 Hom.: 167110 Cov.: 16 AF XY: 0.538 AC XY: 305393 AN XY: 567228

African (AFR) AF: 0.857 AC: 22302 AN: 26028

American (AMR) AF: 0.528 AC: 14874 AN: 28172

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 11954 AN: 18496

East Asian (EAS) AF: 0.340 AC: 12788 AN: 37654

South Asian (SAS) AF: 0.585 AC: 36464 AN: 62334

European-Finnish (FIN) AF: 0.435 AC: 21514 AN: 49428

Middle Eastern (MID) AF: 0.725 AC: 2405 AN: 3316

European-Non Finnish (NFE) AF: 0.535 AC: 464351 AN: 868596

Other (OTH) AF: 0.565 AC: 27549 AN: 48730

GnomAD4 genome AF: 0.614 AC: 93264 AN: 151930 Hom.: 30342 Cov.: 30 AF XY: 0.609 AC XY: 45220 AN XY: 74264

African (AFR) AF: 0.838 AC: 34729 AN: 41440

American (AMR) AF: 0.570 AC: 8704 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2281 AN: 3462

East Asian (EAS) AF: 0.359 AC: 1848 AN: 5150

South Asian (SAS) AF: 0.594 AC: 2861 AN: 4814

European-Finnish (FIN) AF: 0.431 AC: 4549 AN: 10554

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36088 AN: 67944

Other (OTH) AF: 0.631 AC: 1326 AN: 2100

Alfa AF: 0.588 Hom.: 11475

Bravo AF: 0.630

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1126579; hg19: chr2-219000734;