chr4-74038607-G-A

Variant names:

• chr4-74038607-G-A
• rs550117892
• NM_002090.3:c.5C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002090.3(CXCL3):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000758 in 1,319,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A2G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CXCL3 NM_002090.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• Publications: 6 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20344472).

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.5C>T	p.Ala2Val	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.5C>T	p.Ala2Val	missense	Exon 1 of 4	ENSP00000296026.4	P19876
	CXCL3	ENST00000511669.1	TSL:1	n.201C>T		non_coding_transcript_exon	Exon 1 of 2
	CXCL3	ENST00000502974.1	TSL:2	n.83C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000135 AC: 1 AN: 73802 AF XY: 0.0000246

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.58e-7 AC: 1 AN: 1319396 Hom.: 0 Cov.: 30 AF XY: 0.00000154 AC XY: 1 AN XY: 649276

African (AFR) AF: 0.00 AC: 0 AN: 26388

American (AMR) AF: 0.00 AC: 0 AN: 24634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22042

East Asian (EAS) AF: 0.00 AC: 0 AN: 28554

South Asian (SAS) AF: 0.0000143 AC: 1 AN: 69752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4530

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1047724

Other (OTH) AF: 0.00 AC: 0 AN: 54714

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.60
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.071
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.084
MutPred		0.20		Gain of sheet (P = 0.0221)
MVP		0.19
MPC		0.30
ClinPred		0.56	D
GERP RS		0.061
PromoterAI		-0.12	Neutral
Varity_R		0.058
gMVP		0.14
Mutation Taster		=99/1	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: rs550117892; hg19: chr4-74904324;