4-73998280-T-C

Variant names:

• chr4-73998280-T-C
• rs425535
• NM_002994.5:c.168A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002994.5(CXCL5):​c.168A>G​(p.Gln56Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,614,056 control chromosomes in the GnomAD database, including 618,367 homozygotes. 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: 𝑓 0.81 (50996 hom., cov: 33)
  • Exomes 𝑓: 0.88 (567371 hom.)
• Consequence: CXCL5 NM_002994.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.92
• Publications: 44 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:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-5.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL5	NM_002994.5	c.168A>G	p.Gln56Gln	synonymous_variant	Exon 2 of 4	ENST00000296027.5	NP_002985.1
LOC124900715	XR_007058140.1	n.53T>C		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.168A>G	p.Gln56Gln	synonymous_variant	Exon 2 of 4	1	NM_002994.5	ENSP00000296027.4
ENSG00000287037	ENST00000669992.2	n.348T>C		non_coding_transcript_exon_variant	Exon 1 of 3
ENSG00000287037	ENST00000769992.1	n.-125T>C		upstream_gene_variant
ENSG00000287037	ENST00000769993.1	n.-243T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122920 AN: 152078 Hom.: 50999 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.833

GnomAD2 exomes AF: 0.874 AC: 219885 AN: 251456 AF XY: 0.880

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.895

Gnomad ASJ exome AF: 0.860

Gnomad EAS exome AF: 0.967

Gnomad FIN exome AF: 0.882

Gnomad NFE exome AF: 0.886

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.879 AC: 1285649 AN: 1461860 Hom.: 567371 Cov.: 62 AF XY: 0.881 AC XY: 640494 AN XY: 727244

African (AFR) AF: 0.587 AC: 19663 AN: 33480

American (AMR) AF: 0.890 AC: 39802 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 22502 AN: 26136

East Asian (EAS) AF: 0.974 AC: 38659 AN: 39700

South Asian (SAS) AF: 0.904 AC: 77959 AN: 86258

European-Finnish (FIN) AF: 0.887 AC: 47363 AN: 53416

Middle Eastern (MID) AF: 0.853 AC: 4921 AN: 5768

European-Non Finnish (NFE) AF: 0.884 AC: 982492 AN: 1111988

Other (OTH) AF: 0.866 AC: 52288 AN: 60394

GnomAD4 genome AF: 0.808 AC: 122948 AN: 152196 Hom.: 50996 Cov.: 33 AF XY: 0.812 AC XY: 60442 AN XY: 74394

African (AFR) AF: 0.597 AC: 24786 AN: 41506

American (AMR) AF: 0.879 AC: 13457 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3472

East Asian (EAS) AF: 0.968 AC: 4972 AN: 5136

South Asian (SAS) AF: 0.909 AC: 4388 AN: 4828

European-Finnish (FIN) AF: 0.880 AC: 9329 AN: 10606

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60122 AN: 68022

Other (OTH) AF: 0.828 AC: 1748 AN: 2112

Alfa AF: 0.864 Hom.: 123535

Bravo AF: 0.797

Asia WGS AF: 0.870 AC: 3022 AN: 3478

EpiCase AF: 0.886

EpiControl AF: 0.884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.38
PhyloP100		-5.9
PromoterAI		0.0046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs425535; hg19: chr4-74863997; COSMIC: COSV108100268;