rs2302006

Variant names:

• chr7-75813412-T-G
• rs2302006
• NM_002991.3:c.85A>C

Variant summary

Our verdict is Benign. The variant received -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. 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: 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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCL24	NM_002991.3	c.85A>C	p.Ile29Leu	missense_variant	Exon 2 of 3	ENST00000222902.7	NP_002982.2
CCL24	NM_001371193.1	c.85A>C	p.Ile29Leu	missense_variant	Exon 3 of 4		NP_001358122.1
CCL24	XM_011516460.3	c.85A>C	p.Ile29Leu	missense_variant	Exon 5 of 6		XP_011514762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL24	ENST00000222902.7	c.85A>C	p.Ile29Leu	missense_variant	Exon 2 of 3	1	NM_002991.3	ENSP00000222902.2
CCL24	ENST00000416943.1	c.85A>C	p.Ile29Leu	missense_variant	Exon 3 of 4	1		ENSP00000400533.1

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

GnomAD2 exomes AF: 0.286 AC: 71239 AN: 249118 AF XY: 0.278

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 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

African (AFR) AF: 0.283 AC: 9393 AN: 33240

American (AMR) AF: 0.484 AC: 21487 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7356 AN: 26068

East Asian (EAS) AF: 0.555 AC: 21953 AN: 39560

South Asian (SAS) AF: 0.342 AC: 29429 AN: 85986

European-Finnish (FIN) AF: 0.162 AC: 8562 AN: 52970

Middle Eastern (MID) AF: 0.247 AC: 1410 AN: 5700

European-Non Finnish (NFE) AF: 0.186 AC: 205671 AN: 1105048

Other (OTH) AF: 0.251 AC: 15067 AN: 60040

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

African (AFR) AF: 0.280 AC: 11629 AN: 41518

American (AMR) AF: 0.377 AC: 5768 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 980 AN: 3472

East Asian (EAS) AF: 0.567 AC: 2924 AN: 5158

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4826

European-Finnish (FIN) AF: 0.167 AC: 1769 AN: 10602

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12994 AN: 68000

Other (OTH) AF: 0.259 AC: 547 AN: 2114

Alfa AF: 0.224 Hom.: 11316

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
LIST_S2	Benign	0.39	.;T
MetaRNN	Benign	0.00017	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L
PhyloP100		0.17
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
PromoterAI		0.013	Neutral
Varity_R		0.065
gMVP		0.37
Mutation Taster		=98/2	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: rs2302006; hg19: chr7-75442730; COSMIC: COSV56116110;