rs2302005

Variant names:

• chr7-75813441-G-A
• rs2302005
• NM_002991.3:c.74-18C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-75813441-G-A
• chr7-75813441-G-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.74-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,555,160 control chromosomes in the GnomAD database, including 53,564 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.26 (5841 hom., cov: 32)
  • Exomes 𝑓: 0.24 (47723 hom.)
• Consequence: CCL24 NM_002991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 13 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL24	NM_002991.3	c.74-18C>T		intron_variant	Intron 1 of 2	ENST00000222902.7	NP_002982.2
CCL24	NM_001371193.1	c.74-18C>T		intron_variant	Intron 2 of 3		NP_001358122.1
CCL24	XM_011516460.3	c.74-18C>T		intron_variant	Intron 4 of 5		XP_011514762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL24	ENST00000222902.7	c.74-18C>T		intron_variant	Intron 1 of 2	1	NM_002991.3	ENSP00000222902.2
CCL24	ENST00000416943.1	c.74-18C>T		intron_variant	Intron 2 of 3	1		ENSP00000400533.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39405 AN: 152008 Hom.: 5827 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.305 AC: 75479 AN: 247764 AF XY: 0.294

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.652

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.244 AC: 342934 AN: 1403034 Hom.: 47723 Cov.: 24 AF XY: 0.245 AC XY: 171757 AN XY: 701210

African (AFR) AF: 0.244 AC: 7841 AN: 32072

American (AMR) AF: 0.487 AC: 21480 AN: 44138

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7656 AN: 25776

East Asian (EAS) AF: 0.626 AC: 24545 AN: 39230

South Asian (SAS) AF: 0.307 AC: 26038 AN: 84776

European-Finnish (FIN) AF: 0.216 AC: 11406 AN: 52786

Middle Eastern (MID) AF: 0.281 AC: 1535 AN: 5470

European-Non Finnish (NFE) AF: 0.214 AC: 226608 AN: 1060488

Other (OTH) AF: 0.271 AC: 15825 AN: 58298

GnomAD4 genome AF: 0.259 AC: 39435 AN: 152126 Hom.: 5841 Cov.: 32 AF XY: 0.264 AC XY: 19655 AN XY: 74362

African (AFR) AF: 0.242 AC: 10042 AN: 41494

American (AMR) AF: 0.382 AC: 5837 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1029 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3288 AN: 5164

South Asian (SAS) AF: 0.327 AC: 1579 AN: 4824

European-Finnish (FIN) AF: 0.209 AC: 2215 AN: 10588

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14613 AN: 67980

Other (OTH) AF: 0.265 AC: 561 AN: 2114

Alfa AF: 0.237 Hom.: 4781

Bravo AF: 0.276

Asia WGS AF: 0.439 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.66
PhyloP100		-0.019
BranchPoint Hunter		3.0
PromoterAI		-0.0015	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: rs2302005; hg19: chr7-75442759;