rs2230054

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001557.4(CXCR2):c.786C>T(p.Leu262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,613,788 control chromosomes in the GnomAD database, including 196,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22382 hom., cov: 31)

Exomes 𝑓: 0.48 ( 173672 hom. )

Consequence

CXCR2
NM_001557.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.953

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-218135587-C-T is Benign according to our data. Variant chr2-218135587-C-T is described in ClinVar as [Benign]. Clinvar id is 1164812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.953 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCR2	NM_001557.4 linkuse as main transcript	c.786C>T	p.Leu262=	synonymous_variant	3/3	ENST00000318507.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR2	ENST00000318507.7 linkuse as main transcript	c.786C>T	p.Leu262=	synonymous_variant	3/3	1	NM_001557.4	P1

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

80960

AN:

151824

Hom.:

22350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.564

GnomAD3 exomes

AF:

0.483

AC:

121474

AN:

251420

Hom.:

30041

AF XY:

0.485

AC XY:

65836

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.666

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.486

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.518

GnomAD4 exome

AF:

0.484

AC:

707995

AN:

1461846

Hom.:

173672

Cov.:

AF XY:

0.485

AC XY:

352516

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.675

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.566

Gnomad4 EAS exome

AF:

0.317

Gnomad4 SAS exome

AF:

0.485

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.507

GnomAD4 genome

AF:

0.533

AC:

81019

AN:

151942

Hom.:

22382

Cov.:

AF XY:

0.528

AC XY:

39206

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.574

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.499

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.488

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.520

Hom.:

9002

Bravo

AF:

0.546

EpiCase

AF:

0.494

EpiControl

AF:

0.511

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 75% of patients studied by a panel of primary immunodeficiencies. Number of patients: 71. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

Cadd

Benign

2.1

Dann

Benign

0.64

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over