rs3890158

Variant names:

• chr2-218125569-G-A
• rs3890158
• ENST00000453237.5:c.-141+210G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CXCR2	NM_001168298.2	c.-141+210G>A		intron_variant	Intron 1 of 3		NP_001161770.1
CXCR2	XM_047444190.1	c.-89+210G>A		intron_variant	Intron 1 of 2		XP_047300146.1
CXCR2	XM_047444187.1	c.-353G>A		upstream_gene_variant			XP_047300143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000453237.5	c.-141+210G>A		intron_variant	Intron 1 of 3	1		ENSP00000413686.1
CXCR2	ENST00000449014.5	c.-353G>A		upstream_gene_variant		1		ENSP00000410506.1
CXCR2	ENST00000415392.5	c.-282G>A		upstream_gene_variant		5		ENSP00000392348.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.782 AC: 32173 AN: 41138

American (AMR) AF: 0.562 AC: 8547 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2241 AN: 3446

East Asian (EAS) AF: 0.357 AC: 1825 AN: 5112

South Asian (SAS) AF: 0.590 AC: 2805 AN: 4754

European-Finnish (FIN) AF: 0.431 AC: 4498 AN: 10446

Middle Eastern (MID) AF: 0.734 AC: 210 AN: 286

European-Non Finnish (NFE) AF: 0.529 AC: 35799 AN: 67616

Other (OTH) AF: 0.621 AC: 1301 AN: 2096

Alfa AF: 0.575 Hom.: 3468

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
PhyloP100		0.60
PromoterAI		0.033	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3890158; hg19: chr2-218990292;