rs2234671

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000634.3(CXCR1):c.827G>C(p.Ser276Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 1,613,424 control chromosomes in the GnomAD database, including 5,617 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,other (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1228 hom., cov: 32)

Exomes 𝑓: 0.068 ( 4389 hom. )

Consequence

CXCR1
NM_000634.3 missense

Scores

Clinical Significance

Benign; other no assertion criteria provided B:1O:1

Conservation

PhyloP100: 1.04

Publications

77 publications found

Variant links:

Genes affected

CXCR1 (HGNC:6026): (C-X-C motif chemokine receptor 1) 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. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. This gene, IL8RB, 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. [provided by RefSeq, Jul 2008]

CXCR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009817481).

BP6

Variant 2-218164385-C-G is Benign according to our data. Variant chr2-218164385-C-G is described in ClinVar as Benign|other. ClinVar VariationId is 2571396.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR1	NM_000634.3 link	c.827G>C	p.Ser276Thr	missense_variant	Exon 2 of 2	ENST00000295683.3	NP_000625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR1	ENST00000295683.3 link	c.827G>C	p.Ser276Thr	missense_variant	Exon 2 of 2	1	NM_000634.3	ENSP00000295683.2

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16191

AN:

151972

Hom.:

1222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.0774

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0564

Gnomad OTH

AF:

0.0896

GnomAD2 exomes

AF:

0.0910

AC:

22808

AN:

250754

AF XY:

0.0883

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0363

Gnomad EAS exome

AF:

0.0777

Gnomad FIN exome

AF:

0.0567

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0722

GnomAD4 exome

AF:

0.0683

AC:

99797

AN:

1461334

Hom.:

4389

Cov.:

AF XY:

0.0694

AC XY:

50420

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.218

AC:

7298

AN:

33474

American (AMR)

AF:

0.152

AC:

6819

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0356

AC:

928

AN:

26098

East Asian (EAS)

AF:

0.0764

AC:

3033

AN:

39686

South Asian (SAS)

AF:

0.134

AC:

11554

AN:

86232

European-Finnish (FIN)

AF:

0.0583

AC:

3116

AN:

53402

Middle Eastern (MID)

AF:

0.0609

AC:

351

AN:

5762

European-Non Finnish (NFE)

AF:

0.0559

AC:

62185

AN:

1111584

Other (OTH)

AF:

0.0747

AC:

4513

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6876

13752

20628

27504

34380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2558

5116

7674

10232

12790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16214

AN:

152090

Hom.:

1228

Cov.:

AF XY:

0.109

AC XY:

8075

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.204

AC:

8477

AN:

41462

American (AMR)

AF:

0.122

AC:

1871

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3468

East Asian (EAS)

AF:

0.0774

AC:

399

AN:

5158

South Asian (SAS)

AF:

0.144

AC:

695

AN:

4810

European-Finnish (FIN)

AF:

0.0576

AC:

611

AN:

10604

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0564

AC:

3836

AN:

67996

Other (OTH)

AF:

0.0882

AC:

186

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

701

1402

2104

2805

3506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0689

Hom.:

165

Bravo

AF:

0.114

TwinsUK

AF:

0.0472

AC:

175

ALSPAC

AF:

0.0594

AC:

229

ESP6500AA

AF:

0.195

AC:

860

ESP6500EA

AF:

0.0535

AC:

460

ExAC

AF:

0.0913

AC:

11090

Asia WGS

AF:

0.109

AC:

377

AN:

3478

EpiCase

AF:

0.0535

EpiControl

AF:

0.0532

ClinVar

Significance: Benign; other

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CXCR1-related disorder

Benign:1

Dec 09, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Cholangiocarcinoma

Other:1

Dec 10, 2022

Department of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin

Significance:other

Review Status:no assertion criteria provided

Collection Method:research

No association with disease-free or overall survival after resection of intrahepatic Cholangiocarcinoma No association with disease-free or overall survival

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.83

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.045

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0098

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.17

PhyloP100

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

1.3

REVEL

Benign

0.082

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.034

MPC

0.066

ClinPred

0.00018

GERP RS

1.8

Varity_R

0.031

gMVP

0.14

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over