rs2302006

chr7-75813412-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002991.3(CCL24):c.85A>C(p.Ile29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,605,198 control chromosomes in the GnomAD database, including 47,356 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (5570 hom., cov: 32)
  • Exomes 𝑓: 0.22 (41786 hom.)
• Consequence: CCL24 NM_002991.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

Genes affected

CCL24 (HGNC:10623): (C-C motif chemokine ligand 24) This gene belongs to the subfamily of small cytokine CC genes. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity on resting T lymphocytes, a minimal activity on neutrophils, and is negative on monocytes and activated T lymphocytes. This protein also has antimicrobial activity, displaying an antibacterial effect on S. pneumoniae, S. aureus, Non-typeable H. influenzae, and P. aeruginosa. Finally, the protein is a strong suppressor of colony formation by a multipotential hematopoietic progenitor cell line. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.69307E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL24	NM_002991.3	c.85A>C	p.Ile29Leu	missense_variant	2/3	ENST00000222902.7
CCL24	NM_001371193.1	c.85A>C	p.Ile29Leu	missense_variant	3/4
CCL24	XM_011516460.3	c.85A>C	p.Ile29Leu	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL24	ENST00000222902.7	c.85A>C	p.Ile29Leu	missense_variant	2/3	1	NM_002991.3	P1
CCL24	ENST00000416943.1	c.85A>C	p.Ile29Leu	missense_variant	3/4	1		P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38417 AN: 152068 Hom.: 5547 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.259

GnomAD3 exomes AF: 0.286 AC: 71239 AN: 249118 Hom.: 12806 AF XY: 0.278 AC XY: 37397 AN XY: 134686

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.560

Gnomad SAS exome AF: 0.348

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.220 AC: 320328 AN: 1453012 Hom.: 41786 Cov.: 30 AF XY: 0.223 AC XY: 161139 AN XY: 723198

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.555

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.253 AC: 38467 AN: 152186 Hom.: 5570 Cov.: 32 AF XY: 0.258 AC XY: 19205 AN XY: 74402

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.259

Alfa AF: 0.220 Hom.: 7790

Bravo AF: 0.270

TwinsUK AF: 0.197 AC: 732

ALSPAC AF: 0.187 AC: 720

ESP6500AA AF: 0.279 AC: 1230

ESP6500EA AF: 0.201 AC: 1725

ExAC AF: 0.276 AC: 33489

Asia WGS AF: 0.434 AC: 1512 AN: 3478

EpiCase AF: 0.193

EpiControl AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.5
Dann	Benign	0.68
DEOGEN2	Benign	0.083	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.17	N
MetaRNN	Benign	0.00017	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.051
Sift	Benign	0.32	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0040	B;B
Vest4		0.064
MPC		0.17
ClinPred		0.0047	T
GERP RS		-0.41
Varity_R		0.065
gMVP		0.37

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: rs2302006; hg19: chr7-75442730; COSMIC: COSV56116110;