rs6761387

Positions:

• chr2-218131830-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR2	NM_001557.4	c.-26+2465C>T		intron_variant		ENST00000318507.7	NP_001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7	c.-26+2465C>T		intron_variant		1	NM_001557.4	ENSP00000319635	P1

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

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.0317

Gnomad4 SAS AF: 0.0970

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0429

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0556 Hom.: 143

Bravo AF: 0.0795

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.29

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: rs6761387; hg19: chr2-218996553; COSMIC: COSV59281238;