2-218164187-G-A

Variant names:

• chr2-218164187-G-A
• rs16858806
• NM_000634.3:c.1025C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000634.3(CXCR1):​c.1025C>T​(p.Ser342Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00201 in 1,614,070 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (33 hom.)
• Consequence: CXCR1 NM_000634.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.09
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050373077).
• BP6: Variant 2-218164187-G-A is Benign according to our data. Variant chr2-218164187-G-A is described in ClinVar as Benign. ClinVar VariationId is 779083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00975 (1484/152260) while in subpopulation AFR AF = 0.0332 (1381/41540). AF 95% confidence interval is 0.0318. There are 23 homozygotes in GnomAd4. There are 732 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

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.1025C>T	p.Ser342Leu	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.1025C>T	p.Ser342Leu	missense	Exon 2 of 2	ENSP00000295683.2	P25024

Frequencies

GnomAD3 genomes AF: 0.00973 AC: 1480 AN: 152142 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00255 AC: 640 AN: 251202 AF XY: 0.00195

Gnomad AFR exome AF: 0.0342

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00120 AC: 1754 AN: 1461810 Hom.: 33 Cov.: 31 AF XY: 0.00105 AC XY: 766 AN XY: 727206

African (AFR) AF: 0.0358 AC: 1199 AN: 33478

American (AMR) AF: 0.00163 AC: 73 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.000272 AC: 303 AN: 1112000

Other (OTH) AF: 0.00258 AC: 156 AN: 60396

GnomAD4 genome AF: 0.00975 AC: 1484 AN: 152260 Hom.: 23 Cov.: 32 AF XY: 0.00983 AC XY: 732 AN XY: 74442

African (AFR) AF: 0.0332 AC: 1381 AN: 41540

American (AMR) AF: 0.00347 AC: 53 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68022

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00407 Hom.: 19

Bravo AF: 0.0113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0322 AC: 142

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00320 AC: 389

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.1
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.12	T
Polyphen		0.059	B
Vest4		0.20
MVP		0.77
MPC		0.064
ClinPred		0.065	T
GERP RS		3.4
Varity_R		0.24
gMVP		0.19
Mutation Taster		=90/10	polymorphism

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: rs16858806; hg19: chr2-219028910;