Variant 2-218135569-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001557.4(CXCR2):c.768C>T(p.Val256Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 1,614,106 control chromosomes in the GnomAD database, including 1,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 138 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1729 hom. )

Consequence

CXCR2
NM_001557.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.763

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-218135569-C-T is Benign according to our data. Variant chr2-218135569-C-T is described in ClinVar as [Benign]. Clinvar id is 1168916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.763 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR2	NM_001557.4 linkuse as main transcript	c.768C>T	p.Val256Val	synonymous_variant	3/3	ENST00000318507.7	NP_001548.1	P25025Q53PC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7 linkuse as main transcript	c.768C>T	p.Val256Val	synonymous_variant	3/3	1	NM_001557.4	ENSP00000319635.2		P25025

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6224

AN:

152108

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0789

Gnomad EAS

AF:

0.0319

Gnomad SAS

AF:

0.0940

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0431

GnomAD3 exomes

AF:

0.0467

AC:

11732

AN:

251480

Hom.:

352

AF XY:

0.0502

AC XY:

6819

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.0268

Gnomad ASJ exome

AF:

0.0728

Gnomad EAS exome

AF:

0.0341

Gnomad SAS exome

AF:

0.0953

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0502

GnomAD4 exome

AF:

0.0443

AC:

64820

AN:

1461880

Hom.:

1729

Cov.:

AF XY:

0.0462

AC XY:

33591

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0409

Gnomad4 AMR exome

AF:

0.0271

Gnomad4 ASJ exome

AF:

0.0712

Gnomad4 EAS exome

AF:

0.0221

Gnomad4 SAS exome

AF:

0.0957

Gnomad4 FIN exome

AF:

0.0323

Gnomad4 NFE exome

AF:

0.0416

Gnomad4 OTH exome

AF:

0.0488

GnomAD4 genome

AF:

0.0409

AC:

6232

AN:

152226

Hom.:

138

Cov.:

AF XY:

0.0422

AC XY:

3140

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0363

Gnomad4 AMR

AF:

0.0305

Gnomad4 ASJ

AF:

0.0789

Gnomad4 EAS

AF:

0.0320

Gnomad4 SAS

AF:

0.0939

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0423

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0444

Hom.:

Bravo

AF:

0.0385

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

EpiCase

AF:

0.0493

EpiControl

AF:

0.0493

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.034

DANN

Benign

0.72

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