rs6761387

Variant names:

• chr2-218131830-C-T
• rs6761387
• NM_001557.4:c.-26+2465C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001557.4(CXCR2):​c.-26+2465C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 151,316 control chromosomes in the GnomAD database, including 682 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 0.077 (682 hom., cov: 30)
• Consequence: CXCR2 NM_001557.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 9 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: Orphanet, Ambry Genetics

ENSG00000305582 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR2	NM_001557.4	MANE Select	c.-26+2465C>T		intron	N/A	NP_001548.1
	CXCR2	NM_001168298.2		c.-26+2465C>T		intron	N/A	NP_001161770.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR2	ENST00000318507.7	TSL:1 MANE Select	c.-26+2465C>T		intron	N/A	ENSP00000319635.2
	CXCR2	ENST00000453237.5	TSL:1	c.-26+2465C>T		intron	N/A	ENSP00000413686.1
	CXCR2	ENST00000428565.1	TSL:1	c.-26+2465C>T		intron	N/A	ENSP00000392698.1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11594 AN: 151198 Hom.: 677 Cov.: 30

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0429

Gnomad OTH AF: 0.0743

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

GnomAD4 genome AF: 0.0768 AC: 11621 AN: 151316 Hom.: 682 Cov.: 30 AF XY: 0.0776 AC XY: 5737 AN XY: 73900

African (AFR) AF: 0.160 AC: 6559 AN: 41086

American (AMR) AF: 0.0459 AC: 694 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3468

East Asian (EAS) AF: 0.0317 AC: 164 AN: 5172

South Asian (SAS) AF: 0.0970 AC: 463 AN: 4774

European-Finnish (FIN) AF: 0.0332 AC: 348 AN: 10468

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0429 AC: 2914 AN: 67924

Other (OTH) AF: 0.0735 AC: 154 AN: 2094

Alfa AF: 0.0548 Hom.: 156

Bravo AF: 0.0795

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.29
PhyloP100		-0.79
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: rs6761387; hg19: chr2-218996553; COSMIC: COSV59281238;