chr2-218165120-A-C

Variant names:

• chr2-218165120-A-C
• rs16858811
• NM_000634.3:c.92T>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000634.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR1	NM_000634.3	MANE Select	c.92T>G	p.Met31Arg	missense	Exon 2 of 2	NP_000625.1	P25024

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR1	ENST00000295683.3	TSL:1 MANE Select	c.92T>G	p.Met31Arg	missense	Exon 2 of 2	ENSP00000295683.2	P25024

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

GnomAD2 exomes AF: 0.0331 AC: 8320 AN: 251056 AF XY: 0.0339

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 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

African (AFR) AF: 0.0559 AC: 1871 AN: 33480

American (AMR) AF: 0.0216 AC: 968 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 1877 AN: 26136

East Asian (EAS) AF: 0.0159 AC: 630 AN: 39694

South Asian (SAS) AF: 0.0421 AC: 3634 AN: 86258

European-Finnish (FIN) AF: 0.0227 AC: 1212 AN: 53420

Middle Eastern (MID) AF: 0.0362 AC: 209 AN: 5768

European-Non Finnish (NFE) AF: 0.0302 AC: 33616 AN: 1112004

Other (OTH) AF: 0.0365 AC: 2206 AN: 60396

GnomAD4 genome AF: 0.0385 AC: 5867 AN: 152314 Hom.: 121 Cov.: 32 AF XY: 0.0384 AC XY: 2860 AN XY: 74488

African (AFR) AF: 0.0555 AC: 2307 AN: 41564

American (AMR) AF: 0.0254 AC: 389 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.0260 AC: 135 AN: 5188

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4824

European-Finnish (FIN) AF: 0.0261 AC: 277 AN: 10626

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2168 AN: 68018

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0352 Hom.: 485

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 v4.9

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
PhyloP100		-6.2
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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