rs1369446444

Variant names:

• chr7-75811923-T-C
• rs1369446444
• NM_002991.3:c.233A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002991.3(CCL24):​c.233A>G​(p.Lys78Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CCL24 NM_002991.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.944
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06647229).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002991.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL24	NM_002991.3	MANE Select	c.233A>G	p.Lys78Arg	missense	Exon 3 of 3	NP_002982.2
	CCL24	NM_001371193.1		c.233A>G	p.Lys78Arg	missense	Exon 4 of 4	NP_001358122.1	O00175

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL24	ENST00000222902.7	TSL:1 MANE Select	c.233A>G	p.Lys78Arg	missense	Exon 3 of 3	ENSP00000222902.2	O00175
	CCL24	ENST00000416943.1	TSL:1	c.233A>G	p.Lys78Arg	missense	Exon 4 of 4	ENSP00000400533.1	O00175
	CCL24	ENST00000967332.1		c.233A>G	p.Lys78Arg	missense	Exon 6 of 6	ENSP00000637391.1

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148076 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461478 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 148076 Hom.: 0 Cov.: 27 AF XY: 0.0000278 AC XY: 2 AN XY: 71898

African (AFR) AF: 0.00 AC: 0 AN: 39978

American (AMR) AF: 0.00 AC: 0 AN: 14522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 4910

South Asian (SAS) AF: 0.00 AC: 0 AN: 4510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67342

Other (OTH) AF: 0.00 AC: 0 AN: 2014

Alfa AF: 0.0000712 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.0
DANN	Benign	0.93
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.94
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.0080
Sift	Benign	0.13	T
Sift4G	Benign	0.33	T
Polyphen		0.010	B
Vest4		0.14
MutPred		0.43		Loss of methylation at K78 (P = 0.0112)
MVP		0.20
MPC		0.14
ClinPred		0.049	T
GERP RS		-0.93
Varity_R		0.073
gMVP		0.26
Mutation Taster		=99/1	polymorphism

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: rs1369446444; hg19: chr7-75441241;