chr4-73998526-C-A

Variant names:

• chr4-73998526-C-A
• rs768539018
• NM_002994.5:c.56G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002994.5(CXCL5):​c.56G>T​(p.Cys19Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,445,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. C19Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CXCL5 NM_002994.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12484267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL5	NM_002994.5	c.56G>T	p.Cys19Phe	missense_variant	Exon 1 of 4	ENST00000296027.5	NP_002985.1
LOC124900715	XR_007058140.1	n.299C>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL5	ENST00000296027.5	c.56G>T	p.Cys19Phe	missense_variant	Exon 1 of 4	1	NM_002994.5	ENSP00000296027.4
ENSG00000287037	ENST00000669992.1	n.594C>A		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000182 AC: 4 AN: 219434 Hom.: 0 AF XY: 0.0000253 AC XY: 3 AN XY: 118448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000277 AC: 4 AN: 1445082 Hom.: 0 Cov.: 34 AF XY: 0.00000418 AC XY: 3 AN XY: 717322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000957

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.041
Sift	Benign	0.26	T
Sift4G	Benign	0.72	T
Polyphen		0.94	P
Vest4		0.27
MutPred		0.42		Loss of glycosylation at P14 (P = 0.0411);
MVP		0.28
MPC		0.53
ClinPred		0.50	D
GERP RS		1.5
Varity_R		0.12
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs768539018; hg19: chr4-74864243;