NM_002090.3:c.50G>A

Variant names:

• chr4-74038562-C-T
• rs1313005912
• NM_002090.3:c.50G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002090.3(CXCL3):​c.50G>A​(p.Arg17Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,338,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CXCL3 NM_002090.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 0 publications found

Genes affected

CXCL3 (HGNC:4604): (C-X-C motif chemokine ligand 3) This antimicrobial gene encodes a member of the CXC subfamily of chemokines. The encoded protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2. This protein plays a role in inflammation and as a chemoattractant for neutrophils. [provided by RefSeq, Sep 2014]

ENSG00000287037 (HGNC:58815):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066589475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002090.3. 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
	CXCL3	NM_002090.3	MANE Select	c.50G>A	p.Arg17Gln	missense	Exon 1 of 4	NP_002081.2	P19876

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL3	ENST00000296026.4	TSL:1 MANE Select	c.50G>A	p.Arg17Gln	missense	Exon 1 of 4	ENSP00000296026.4	P19876
	CXCL3	ENST00000511669.1	TSL:1	n.246G>A		non_coding_transcript_exon	Exon 1 of 2
	CXCL3	ENST00000502974.1	TSL:2	n.128G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1338304 Hom.: 0 Cov.: 30 AF XY: 0.00000152 AC XY: 1 AN XY: 658948

African (AFR) AF: 0.00 AC: 0 AN: 26912

American (AMR) AF: 0.00 AC: 0 AN: 27358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22958

East Asian (EAS) AF: 0.00 AC: 0 AN: 28668

South Asian (SAS) AF: 0.00 AC: 0 AN: 72122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4850

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1053688

Other (OTH) AF: 0.00 AC: 0 AN: 55344

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.8
DANN	Benign	0.95
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.31
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.033
Sift	Benign	0.17	T
Sift4G	Benign	0.48	T
Polyphen		0.034	B
Vest4		0.060
MutPred		0.43		Loss of MoRF binding (P = 0.0262)
MVP		0.014
MPC		0.047
ClinPred		0.16	T
GERP RS		0.87
PromoterAI		-0.39	Neutral
Varity_R		0.026
gMVP		0.085
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1313005912; hg19: chr4-74904279;