chr7-75813441-G-A

Variant names:

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

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

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

Gnomad4 AFR exome AF: 0.244 AC: 7841 AN: 32072

Gnomad4 AMR exome AF: 0.487 AC: 21480 AN: 44138

Gnomad4 ASJ exome AF: 0.297 AC: 7656 AN: 25776

Gnomad4 EAS exome AF: 0.626 AC: 24545 AN: 39230

Gnomad4 SAS exome AF: 0.307 AC: 26038 AN: 84776

Gnomad4 FIN exome AF: 0.216 AC: 11406 AN: 52786

Gnomad4 NFE exome AF: 0.214 AC: 226608 AN: 1060488

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.242 AC: 0.242011 AN: 0.242011

Gnomad4 AMR AF: 0.382 AC: 0.381903 AN: 0.381903

Gnomad4 ASJ AF: 0.296 AC: 0.296371 AN: 0.296371

Gnomad4 EAS AF: 0.637 AC: 0.636716 AN: 0.636716

Gnomad4 SAS AF: 0.327 AC: 0.327322 AN: 0.327322

Gnomad4 FIN AF: 0.209 AC: 0.209199 AN: 0.209199

Gnomad4 NFE AF: 0.215 AC: 0.21496 AN: 0.21496

Gnomad4 OTH AF: 0.265 AC: 0.265374 AN: 0.265374

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
BranchPoint Hunter		3.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs2302005; hg19: chr7-75442759;