chr2-218125863-C-T

Position:

• chr2-218125863-C-T

Variant summary

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

The NM_001168298.2(CXCR2):​c.-140-428C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,340 control chromosomes in the GnomAD database, including 19,169 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 0.50 (19101 hom., cov: 29)
  • Exomes 𝑓: 0.44 (68 hom.)
• Consequence: CXCR2 NM_001168298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR2	XM_047444189.1	c.-149C>T		5_prime_UTR_variant	1/4		XP_047300145.1
CXCR2	NM_001168298.2	c.-140-428C>T		intron_variant			NP_001161770.1
CXCR2	XM_047444187.1	c.-141+82C>T		intron_variant			XP_047300143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000453237.5	c.-140-428C>T		intron_variant		1		ENSP00000413686.1
CXCR2	ENST00000449014.5	c.-141+82C>T		intron_variant		1		ENSP00000410506.1
CXCR2	ENST00000415392.5	c.-141+153C>T		intron_variant		5		ENSP00000392348.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75493 AN: 151614 Hom.: 19080 Cov.: 29

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.442 AC: 269 AN: 608 Hom.: 68 Cov.: 0 AF XY: 0.454 AC XY: 168 AN XY: 370

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.498 AC: 75533 AN: 151732 Hom.: 19101 Cov.: 29 AF XY: 0.493 AC XY: 36581 AN XY: 74170

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.532

Alfa AF: 0.503 Hom.: 3984

Bravo AF: 0.506

Asia WGS AF: 0.392 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4674258; hg19: chr2-218990586;