rs16858811

chr2-218165120-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.15

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]

ACMG classification

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/exons	MANE	UniProt
CXCR1	NM_000634.3	c.92T>G	p.Met31Arg	missense_variant	2/2	ENST00000295683.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR1	ENST00000295683.3	c.92T>G	p.Met31Arg	missense_variant	2/2	1	NM_000634.3	P1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5863 AN: 152196 Hom.: 121 Cov.: 32

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

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.: 32 AF XY: 0.0323 AC XY: 23498 AN XY: 727238

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.: 32 AF XY: 0.0384 AC XY: 2860 AN XY: 74488

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	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.0010
Dann	Benign	0.15
DEOGEN2	Benign	0.040	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00081	N
LIST_S2	Benign	0.040	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.16
Sift	Benign	0.99	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.11
ClinPred		0.0080	T
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

Other links and lift over

dbSNP: rs16858811; hg19: chr2-219029843; COSMIC: COSV55281268;