rs1126580

Positions:

• chr2-218136243-G-A
• chr2-218136243-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001557.4(CXCR2):​c.*359G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 191,236 control chromosomes in the GnomAD database, including 16,342 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 0.42 (13386 hom., cov: 27)
  • Exomes 𝑓: 0.36 (2956 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR2	NM_001557.4	c.*359G>A		3_prime_UTR_variant	3/3	ENST00000318507.7	NP_001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7	c.*359G>A		3_prime_UTR_variant	3/3	1	NM_001557.4	ENSP00000319635.2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 62514 AN: 149926 Hom.: 13373 Cov.: 27

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.356 AC: 14646 AN: 41198 Hom.: 2956 Cov.: 0 AF XY: 0.357 AC XY: 7266 AN XY: 20372

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.417 AC: 62543 AN: 150038 Hom.: 13386 Cov.: 27 AF XY: 0.410 AC XY: 29978 AN XY: 73120

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.461

Alfa AF: 0.438 Hom.: 23802

Bravo AF: 0.422

Asia WGS AF: 0.305 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs1126580; hg19: chr2-219000966;