Variant rs45606837 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001557.4(CXCR2):c.936C>T(p.Leu312Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,614,158 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 31)

Exomes 𝑓: 0.013 ( 201 hom. )

Consequence

CXCR2
NM_001557.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.595

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=-0.42).

BP6

Variant 2-218135737-C-T is Benign according to our data. Variant chr2-218135737-C-T is described in ClinVar as [Benign]. Clinvar id is 1164697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.595 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0102 (1558/152270) while in subpopulation SAS AF= 0.0384 (185/4816). AF 95% confidence interval is 0.0339. There are 16 homozygotes in gnomad4. There are 852 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR2	NM_001557.4 link	c.936C>T	p.Leu312Leu	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 link	c.936C>T	p.Leu312Leu	synonymous_variant	3/3	1	NM_001557.4	ENSP00000319635.2		P25025

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1560

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0388

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.0137

AC:

3434

AN:

251476

Hom.:

AF XY:

0.0156

AC XY:

2118

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0346

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.0126

AC:

18440

AN:

1461888

Hom.:

201

Cov.:

AF XY:

0.0135

AC XY:

9847

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.0152

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.0188

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0102

AC:

1558

AN:

152270

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

852

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0384

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00787

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0151

EpiControl

AF:

0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

-0.42

CADD

Benign

7.9

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