Variant chr2-218136222-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.377

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0272

AC XY:

996

AN XY:

36642

show subpopulations

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.:

Cov.:

AF XY:

0.0253

AC XY:

1878

AN XY:

74314

show subpopulations

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.:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over