rs1126579

chr2-218136011-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001557.4(CXCR2):c.*127T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,294,684 control chromosomes in the GnomAD database, including 197,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (30342 hom., cov: 30)
  • Exomes 𝑓: 0.54 (167110 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.752

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-218136011-T-C is Benign according to our data. Variant chr2-218136011-T-C is described in ClinVar as [Benign]. Clinvar id is 1222897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCR2	NM_001557.4	c.*127T>C		3_prime_UTR_variant	3/3	ENST00000318507.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR2	ENST00000318507.7	c.*127T>C		3_prime_UTR_variant	3/3	1	NM_001557.4	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93167 AN: 151812 Hom.: 30290 Cov.: 30

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.537 AC: 614201 AN: 1142754 Hom.: 167110 Cov.: 16 AF XY: 0.538 AC XY: 305393 AN XY: 567228

Gnomad4 AFR exome AF: 0.857

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.614 AC: 93264 AN: 151930 Hom.: 30342 Cov.: 30 AF XY: 0.609 AC XY: 45220 AN XY: 74264

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.631

Alfa AF: 0.606 Hom.: 7344

Bravo AF: 0.630

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

This variant is associated with the following publications: (PMID: 23615182, 25480945) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.51

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: rs1126579; hg19: chr2-219000734;