2-218165354-G-A

Variant names:

• chr2-218165354-G-A
• rs16858816
• NM_000634.3:c.-33-110C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000634.3(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 NM_000634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR1	NM_000634.3	MANE Select	c.-33-110C>T		intron	N/A	NP_000625.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR1	ENST00000295683.3	TSL:1 MANE Select	c.-33-110C>T		intron	N/A	ENSP00000295683.2

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

African (AFR) AF: 0.0554 AC: 998 AN: 18000

American (AMR) AF: 0.0221 AC: 754 AN: 34086

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 1376 AN: 19242

East Asian (EAS) AF: 0.0149 AC: 492 AN: 33048

South Asian (SAS) AF: 0.0365 AC: 2292 AN: 62742

European-Finnish (FIN) AF: 0.0234 AC: 803 AN: 34344

Middle Eastern (MID) AF: 0.0391 AC: 113 AN: 2888

European-Non Finnish (NFE) AF: 0.0320 AC: 13900 AN: 434974

Other (OTH) AF: 0.0367 AC: 1257 AN: 34244

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

African (AFR) AF: 0.0553 AC: 2297 AN: 41560

American (AMR) AF: 0.0252 AC: 386 AN: 15298

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

East Asian (EAS) AF: 0.0260 AC: 135 AN: 5184

South Asian (SAS) AF: 0.0360 AC: 174 AN: 4830

European-Finnish (FIN) AF: 0.0259 AC: 275 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0319 AC: 2168 AN: 68020

Other (OTH) AF: 0.0380 AC: 80 AN: 2108

Alfa AF: 0.0266 Hom.: 29

Bravo AF: 0.0376

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-0.71
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: rs16858816; hg19: chr2-219030077;