rs2234671

Variant names:

• chr2-218164385-C-G
• rs2234671
• NM_000634.3:c.827G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-218164385-C-G
• chr2-218164385-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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
• Clinical Significance: Benign; other no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: 1.04
• Publications: 77 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 -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.

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.827G>C	p.Ser276Thr	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.827G>C	p.Ser276Thr	missense	Exon 2 of 2	ENSP00000295683.2	P25024

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16191 AN: 151972 Hom.: 1222 Cov.: 32

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

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.: 32 AF XY: 0.0694 AC XY: 50420 AN XY: 726914

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

GnomAD4 genome AF: 0.107 AC: 16214 AN: 152090 Hom.: 1228 Cov.: 32 AF XY: 0.109 AC XY: 8075 AN XY: 74356

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: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3836 AN: 67996

Other (OTH) AF: 0.0882 AC: 186 AN: 2110

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

ClinVar submissions

Significance: Benign; other

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CXCR1-related disorder (1)
-	-	-	Cholangiocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.83
DANN	Benign	0.14
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.17	N
PhyloP100		1.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.082
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.034
MPC		0.066
ClinPred		0.00018	T
GERP RS		1.8
Varity_R		0.031
gMVP		0.14
Mutation Taster		=90/10	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: rs2234671; hg19: chr2-219029108; COSMIC: COSV55281069;