dbSNP rs1126579: CXCR2:c.*127T>C (chr2-218136011-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001557.4(CXCR2):c.*127T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,294,684 control chromosomes in the GnomAD database, including 197,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 30342 hom., cov: 30)

Exomes 𝑓: 0.54 ( 167110 hom. )

Consequence

CXCR2
NM_001557.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.752

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-218136011-T-C is Benign according to our data. Variant chr2-218136011-T-C is described in ClinVar as [Benign]. Clinvar id is 1222897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR2	NM_001557.4 link	c.*127T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000318507.7	NP_001548.1	P25025Q53PC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR2	ENST00000318507.7 link	c.*127T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001557.4	ENSP00000319635.2		P25025

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93167

AN:

151812

Hom.:

30290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.838

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.633

GnomAD4 exome

AF:

0.537

AC:

614201

AN:

1142754

Hom.:

167110

Cov.:

AF XY:

0.538

AC XY:

305393

AN XY:

567228

show subpopulations

Gnomad4 AFR exome

AF:

0.857

Gnomad4 AMR exome

AF:

0.528

Gnomad4 ASJ exome

AF:

0.646

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.585

Gnomad4 FIN exome

AF:

0.435

Gnomad4 NFE exome

AF:

0.535

Gnomad4 OTH exome

AF:

0.565

GnomAD4 genome

AF:

0.614

AC:

93264

AN:

151930

Hom.:

30342

Cov.:

AF XY:

0.609

AC XY:

45220

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.838

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.659

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.594

Gnomad4 FIN

AF:

0.431

Gnomad4 NFE

AF:

0.531

Gnomad4 OTH

AF:

0.631

Alfa

AF:

0.606

Hom.:

7344

Bravo

AF:

0.630

Asia WGS

AF:

0.497

AC:

1727

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23615182, 25480945) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

DANN

Benign

0.51

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