rs13306441

Positions:

• chr2-218136222-A-G

Variant summary

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

The NM_001557.4(CXCR2):​c.*338A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 225,106 control chromosomes in the GnomAD database, including 97 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 0.025 (56 hom., cov: 30)
  • Exomes 𝑓: 0.026 (41 hom.)
• Consequence: CXCR2 NM_001557.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

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=-0.86).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0246 (3743/152010) while in subpopulation SAS AF= 0.0479 (230/4798). AF 95% confidence interval is 0.0429. There are 56 homozygotes in gnomad4. There are 1878 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR2	NM_001557.4	c.*338A>G		3_prime_UTR_variant	3/3	ENST00000318507.7	NP_001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7	c.*338A>G		3_prime_UTR_variant	3/3	1	NM_001557.4	ENSP00000319635	P1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3741 AN: 151892 Hom.: 56 Cov.: 30

Gnomad AFR AF: 0.00620

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0332

GnomAD4 exome AF: 0.0262 AC: 1918 AN: 73096 Hom.: 41 Cov.: 0 AF XY: 0.0272 AC XY: 996 AN XY: 36642

Gnomad4 AFR exome AF: 0.00580

Gnomad4 AMR exome AF: 0.0222

Gnomad4 ASJ exome AF: 0.0514

Gnomad4 EAS exome AF: 0.0118

Gnomad4 SAS exome AF: 0.0452

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.0291

Gnomad4 OTH exome AF: 0.0290

GnomAD4 genome AF: 0.0246 AC: 3743 AN: 152010 Hom.: 56 Cov.: 30 AF XY: 0.0253 AC XY: 1878 AN XY: 74314

Gnomad4 AFR AF: 0.00620

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.0257

Gnomad4 SAS AF: 0.0479

Gnomad4 FIN AF: 0.0260

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0329

Alfa AF: 0.0329 Hom.: 97

Bravo AF: 0.0226

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.40

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: rs13306441; hg19: chr2-219000945;