4-74038607-G-T

Variant names:

• chr4-74038607-G-T
• rs550117892
• NM_002090.3:c.5C>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.5C>A​(p.Ala2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,332 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: 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=0.008619249).

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>A	p.Ala2Asp	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>A	p.Ala2Asp	missense	Exon 1 of 4	ENSP00000296026.4	P19876
	CXCL3	ENST00000511669.1	TSL:1	n.201C>A		non_coding_transcript_exon	Exon 1 of 2
	CXCL3	ENST00000502974.1	TSL:2	n.83C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000135 AC: 1 AN: 73802 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000493

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1319398 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 69752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41060

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 AF: 0.00000656 AC: 1 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ExAC AF: 0.0000132 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T
Eigen	Benign	0.054
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.60
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.14		Gain of loop (P = 0.0502)
MVP		0.29
MPC		0.35
ClinPred		0.57	D
GERP RS		0.061
PromoterAI		-0.045	Neutral
Varity_R		0.22
gMVP		0.21
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;