rs3890158

chr2-218125569-G-A

Variant summary

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

The ENST00000453237.5(CXCR2):c.-141+210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,012 control chromosomes in the GnomAD database, including 28,082 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 0.60 (28081 hom., cov: 29)
  • Exomes 𝑓: 0.39 (1 hom.)
• Consequence: CXCR2 ENST00000453237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCR2	NM_001168298.2	c.-141+210G>A		intron_variant
CXCR2	XM_047444190.1	c.-89+210G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR2	ENST00000453237.5	c.-141+210G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 89978 AN: 150874 Hom.: 28047 Cov.: 29

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.389 AC: 7 AN: 18 Hom.: 1 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.596 AC: 90051 AN: 150994 Hom.: 28081 Cov.: 29 AF XY: 0.591 AC XY: 43606 AN XY: 73738

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.621

Alfa AF: 0.572 Hom.: 3225

Bravo AF: 0.612

Asia WGS AF: 0.481 AC: 1671 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.0
Dann	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3890158; hg19: chr2-218990292;