rs17844765

Positions:

• chr2-218136239-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001557.4(CXCR2):​c.*355C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 199,492 control chromosomes in the GnomAD database, including 29 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 0.016 (25 hom., cov: 30)
  • Exomes 𝑓: 0.0096 (4 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789

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=-0.98).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0159 (2351/147718) while in subpopulation SAS AF= 0.0461 (214/4638). AF 95% confidence interval is 0.0411. There are 25 homozygotes in gnomad4. There are 1177 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCR2	NM_001557.4	c.*355C>T		3_prime_UTR_variant	3/3	ENST00000318507.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR2	ENST00000318507.7	c.*355C>T		3_prime_UTR_variant	3/3	1	NM_001557.4	P1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2345 AN: 147620 Hom.: 24 Cov.: 30

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00866

Gnomad ASJ AF: 0.00901

Gnomad EAS AF: 0.00235

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0104

GnomAD4 exome AF: 0.00956 AC: 495 AN: 51774 Hom.: 4 Cov.: 0 AF XY: 0.0108 AC XY: 279 AN XY: 25718

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.00193

Gnomad4 SAS exome AF: 0.0446

Gnomad4 FIN exome AF: 0.00895

Gnomad4 NFE exome AF: 0.00864

Gnomad4 OTH exome AF: 0.00822

GnomAD4 genome AF: 0.0159 AC: 2351 AN: 147718 Hom.: 25 Cov.: 30 AF XY: 0.0164 AC XY: 1177 AN XY: 71790

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.00865

Gnomad4 ASJ AF: 0.00901

Gnomad4 EAS AF: 0.00216

Gnomad4 SAS AF: 0.0461

Gnomad4 FIN AF: 0.00735

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0103

Alfa AF: 0.0116 Hom.: 14

Bravo AF: 0.0150

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.34

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: rs17844765; hg19: chr2-219000962;