2-218165354-G-A

Position:

• chr2-218165354-G-A

Variant summary

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

The ENST00000295683.3(CXCR1):​c.-33-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 825,858 control chromosomes in the GnomAD database, including 557 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 0.038 (119 hom., cov: 32)
  • Exomes 𝑓: 0.033 (438 hom.)
• Consequence: CXCR1 ENST00000295683.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR1	NM_000634.3	c.-33-110C>T		intron_variant		ENST00000295683.3	NP_000625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR1	ENST00000295683.3	c.-33-110C>T		intron_variant		1	NM_000634.3	ENSP00000295683	P1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5829 AN: 152172 Hom.: 119 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0326 AC: 21985 AN: 673568 Hom.: 438 AF XY: 0.0334 AC XY: 11865 AN XY: 355348

Gnomad4 AFR exome AF: 0.0554

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.0715

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.0365

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0320

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0383 AC: 5833 AN: 152290 Hom.: 119 Cov.: 32 AF XY: 0.0381 AC XY: 2837 AN XY: 74466

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0259

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0380

Alfa AF: 0.0218 Hom.: 15

Bravo AF: 0.0376

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63

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: rs16858816; hg19: chr2-219030077;