chr2-218162779-G-C

Variant names:

• chr2-218162779-G-C
• rs2854386
• NM_000634.3:c.*1380C>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.*1380C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,524 control chromosomes in the GnomAD database, including 57,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (57807 hom., cov: 34)
  • Exomes 𝑓: 0.92 (105 hom.)
• Consequence: CXCR1 NM_000634.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 20 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 (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR1	NM_000634.3	c.*1380C>G		downstream_gene_variant		ENST00000295683.3	NP_000625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR1	ENST00000295683.3	c.*1380C>G		downstream_gene_variant		1	NM_000634.3	ENSP00000295683.2

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131621 AN: 152158 Hom.: 57775 Cov.: 34

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.891

GnomAD4 exome AF: 0.919 AC: 228 AN: 248 Hom.: 105 AF XY: 0.917 AC XY: 132 AN XY: 144

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.935 AC: 129 AN: 138

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.948 AC: 55 AN: 58

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.909 AC: 40 AN: 44

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.865 AC: 131704 AN: 152276 Hom.: 57807 Cov.: 34 AF XY: 0.863 AC XY: 64299 AN XY: 74478

African (AFR) AF: 0.698 AC: 28979 AN: 41502

American (AMR) AF: 0.865 AC: 13231 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3362 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4784 AN: 5188

South Asian (SAS) AF: 0.848 AC: 4096 AN: 4828

European-Finnish (FIN) AF: 0.942 AC: 10014 AN: 10626

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64177 AN: 68042

Other (OTH) AF: 0.893 AC: 1886 AN: 2112

Alfa AF: 0.895 Hom.: 7637

Bravo AF: 0.853

Asia WGS AF: 0.880 AC: 3060 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.31
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2854386; hg19: chr2-219027502;