4-74099033-G-C

Variant names:

• chr4-74099033-G-C
• rs907204082
• NM_002089.4:c.88C>G

Variant summary

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

The NM_002089.4(CXCL2):​c.88C>G​(p.Arg30Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CXCL2 NM_002089.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457
• Publications: 0 publications found

Genes affected

CXCL2 (HGNC:4603): (C-X-C motif chemokine ligand 2) This antimicrobial gene is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CXC subfamily, is expressed at sites of inflammation and may suppress hematopoietic progenitor cell proliferation. [provided by RefSeq, Sep 2014]

ENSG00000289241 (HGNC:):

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=0.17739204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002089.4. 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
	CXCL2	NM_002089.4	MANE Select	c.88C>G	p.Arg30Gly	missense	Exon 1 of 4	NP_002080.1	P19875

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL2	ENST00000508487.3	TSL:1 MANE Select	c.88C>G	p.Arg30Gly	missense	Exon 1 of 4	ENSP00000427279.1	P19875
	CXCL2	ENST00000296031.4	TSL:1	n.163C>G		non_coding_transcript_exon	Exon 1 of 3
	CXCL2	ENST00000906203.1		c.88C>G	p.Arg30Gly	missense	Exon 1 of 4	ENSP00000576262.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.46
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.17
Sift	Benign	0.041	D
Sift4G	Benign	0.39	T
Polyphen		0.36	B
Vest4		0.18
MutPred		0.49		Loss of helix (P = 0.0072)
MVP		0.31
MPC		0.44
ClinPred		0.12	T
GERP RS		1.8
PromoterAI		-0.15	Neutral
Varity_R		0.093
gMVP		0.12
Mutation Taster		=100/0	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: rs907204082; hg19: chr4-74964750;