chr4-74099081-G-T

Variant names:

• chr4-74099081-G-T
• rs747593102
• NM_002089.4:c.40C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002089.4(CXCL2):​c.40C>A​(p.Arg14Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000298 in 1,343,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: CXCL2 NM_002089.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.

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.40C>A	p.Arg14Arg	synonymous	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.40C>A	p.Arg14Arg	synonymous	Exon 1 of 4	ENSP00000427279.1	P19875
	CXCL2	ENST00000296031.4	TSL:1	n.115C>A		non_coding_transcript_exon	Exon 1 of 3
	CXCL2	ENST00000906203.1		c.40C>A	p.Arg14Arg	synonymous	Exon 1 of 4	ENSP00000576262.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000298 AC: 4 AN: 1343076 Hom.: 0 Cov.: 30 AF XY: 0.00000604 AC XY: 4 AN XY: 661726

African (AFR) AF: 0.00 AC: 0 AN: 27034

American (AMR) AF: 0.00 AC: 0 AN: 28270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23346

East Asian (EAS) AF: 0.00 AC: 0 AN: 28712

South Asian (SAS) AF: 0.0000544 AC: 4 AN: 73480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4866

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055756

Other (OTH) AF: 0.00 AC: 0 AN: 55550

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.9
DANN	Benign	0.70
PhyloP100		-2.2
PromoterAI		-0.076	Neutral

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: rs747593102; hg19: chr4-74964798;