dbSNP rs16858811: CXCR1:p.Met31Arg (chr2-218165120-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000634.3(CXCR1):c.92T>G(p.Met31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,614,194 control chromosomes in the GnomAD database, including 1,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.039 ( 121 hom., cov: 32)

Exomes 𝑓: 0.032 ( 889 hom. )

Consequence

CXCR1
NM_000634.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.15

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024679005).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR1	NM_000634.3 link	c.92T>G	p.Met31Arg	missense_variant	Exon 2 of 2	ENST00000295683.3	NP_000625.1	P25024

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR1	ENST00000295683.3 link	c.92T>G	p.Met31Arg	missense_variant	Exon 2 of 2	1	NM_000634.3	ENSP00000295683.2		P25024

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5863

AN:

152196

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0555

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0254

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.0258

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0388

GnomAD3 exomes

AF:

0.0331

AC:

8320

AN:

251056

Hom.:

151

AF XY:

0.0339

AC XY:

4597

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.0559

Gnomad AMR exome

AF:

0.0215

Gnomad ASJ exome

AF:

0.0720

Gnomad EAS exome

AF:

0.0258

Gnomad SAS exome

AF:

0.0389

Gnomad FIN exome

AF:

0.0228

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0368

GnomAD4 exome

AF:

0.0316

AC:

46223

AN:

1461880

Hom.:

889

Cov.:

AF XY:

0.0323

AC XY:

23498

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0718

Gnomad4 EAS exome

AF:

0.0159

Gnomad4 SAS exome

AF:

0.0421

Gnomad4 FIN exome

AF:

0.0227

Gnomad4 NFE exome

AF:

0.0302

Gnomad4 OTH exome

AF:

0.0365

GnomAD4 genome

AF:

0.0385

AC:

5867

AN:

152314

Hom.:

121

Cov.:

AF XY:

0.0384

AC XY:

2860

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0555

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.0260

Gnomad4 SAS

AF:

0.0400

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0319

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0362

Hom.:

240

Bravo

AF:

0.0377

TwinsUK

AF:

0.0280

AC:

104

ALSPAC

AF:

0.0270

AC:

104

ESP6500AA

AF:

0.0552

AC:

243

ESP6500EA

AF:

0.0327

AC:

281

ExAC

AF:

0.0334

AC:

4056

Asia WGS

AF:

0.0590

AC:

205

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0010

DANN

Benign

0.15

DEOGEN2

Benign

0.040

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00081

LIST_S2

Benign

0.040

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.20

PROVEAN

Benign

1.5

REVEL

Benign

0.16

Sift

Benign

0.99

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.028

MPC

0.11

ClinPred

0.0080

GERP RS

-11

Varity_R

0.16

gMVP

0.25

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over