chr2-218164385-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,other (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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 -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 id 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	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	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.: 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

GnomAD3 exomes AF: 0.0910 AC: 22808 AN: 250754 Hom.: 1451 AF XY: 0.0883 AC XY: 11965 AN XY: 135506

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 SAS exome AF: 0.139

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

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.0356

Gnomad4 EAS exome AF: 0.0764

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0583

Gnomad4 NFE exome AF: 0.0559

Gnomad4 OTH exome AF: 0.0747

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

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0774

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0576

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0882

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:1 Other:1

Revision: no assertion criteria provided

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	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
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

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: rs2234671; hg19: chr2-219029108; COSMIC: COSV55281069;