4-73998240-C-A

Variant names:

• chr4-73998240-C-A
• rs200635427
• NM_002994.5:c.208G>T

Variant summary

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

The NM_002994.5(CXCL5):​c.208G>T​(p.Ala70Ser) 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. 16/22 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. A70T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CXCL5 NM_002994.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 1 publications found

Genes affected

CXCL5 (HGNC:10642): (C-X-C motif chemokine ligand 5) This gene encodes a protein that is a member of the CXC subfamily of chemokines. Chemokines, which recruit and activate leukocytes, are classified by function (inflammatory or homeostatic) or by structure. This protein is proposed to bind the G-protein coupled receptor chemokine (C-X-C motif) receptor 2 to recruit neutrophils, to promote angiogenesis and to remodel connective tissues. This protein is thought to play a role in cancer cell proliferation, migration, and invasion. [provided by RefSeq, May 2013]

ENSG00000287037 (HGNC:58815):

LOC124900715 (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=0.09925982).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002994.5. 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
	CXCL5	NM_002994.5	MANE Select	c.208G>T	p.Ala70Ser	missense	Exon 2 of 4	NP_002985.1	Q6I9S7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL5	ENST00000296027.5	TSL:1 MANE Select	c.208G>T	p.Ala70Ser	missense	Exon 2 of 4	ENSP00000296027.4	P42830
	ENSG00000287037	ENST00000669992.2		n.308C>A		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000287037	ENST00000769992.1		n.-165C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.5
DANN	Benign	0.95
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.082	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.40
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.017
Sift	Benign	0.28	T
Sift4G	Benign	0.52	T
Polyphen		0.85	P
Vest4		0.078
MutPred		0.36		Loss of catalytic residue at A70 (P = 0.0849)
MVP		0.16
MPC		0.31
ClinPred		0.26	T
GERP RS		0.75
PromoterAI		-0.092	Neutral
Varity_R		0.13
gMVP		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs200635427; hg19: chr4-74863957;