chr4-73998290-T-C

Position:

• chr4-73998290-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002994.5(CXCL5):​c.158A>G​(p.Gln53Arg) 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. 15/21 in silico tools predict 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)
• Consequence: CXCL5 NM_002994.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.85

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046216458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL5	NM_002994.5	c.158A>G	p.Gln53Arg	missense_variant	2/4	ENST00000296027.5	NP_002985.1
LOC124900715	XR_007058140.1	n.63T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL5	ENST00000296027.5	c.158A>G	p.Gln53Arg	missense_variant	2/4	1	NM_002994.5	ENSP00000296027.4
ENSG00000287037	ENST00000669992.1	n.358T>C		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.158A>G (p.Q53R) alteration is located in exon 2 (coding exon 2) of the CXCL5 gene. This alteration results from a A to G substitution at nucleotide position 158, causing the glutamine (Q) at amino acid position 53 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.63
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.0060
Sift	Benign	0.31	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.45		Gain of MoRF binding (P = 0.0654);
MVP		0.14
MPC		0.10
ClinPred		0.16	T
GERP RS		-7.6
Varity_R		0.072
gMVP		0.096

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-74864007;