rs2302004

Positions:

• chr7-75813537-A-G
• chr7-75813537-A-T

Variant summary

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

The NM_002991.3(CCL24):​c.73+106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,253,546 control chromosomes in the GnomAD database, including 126,459 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 0.45 (15487 hom., cov: 32)
  • Exomes 𝑓: 0.44 (110972 hom.)
• Consequence: CCL24 NM_002991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL24	NM_002991.3	c.73+106T>C		intron_variant		ENST00000222902.7	NP_002982.2
CCL24	NM_001371193.1	c.73+106T>C		intron_variant			NP_001358122.1
CCL24	XM_011516460.3	c.73+106T>C		intron_variant			XP_011514762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL24	ENST00000222902.7	c.73+106T>C		intron_variant		1	NM_002991.3	ENSP00000222902	P1
CCL24	ENST00000416943.1	c.73+106T>C		intron_variant		1		ENSP00000400533	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67838 AN: 151860 Hom.: 15458 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.443 AC: 487809 AN: 1101568 Hom.: 110972 Cov.: 15 AF XY: 0.442 AC XY: 247855 AN XY: 561370

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.495

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.447 AC: 67910 AN: 151978 Hom.: 15487 Cov.: 32 AF XY: 0.451 AC XY: 33520 AN XY: 74296

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.425

Alfa AF: 0.426 Hom.: 11904

Bravo AF: 0.450

Asia WGS AF: 0.538 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.48

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: rs2302004; hg19: chr7-75442855; COSMIC: COSV56116266;