Genetic Variant CCL24:p.Ala104Ser (chr7-75811846-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002991.3(CCL24):c.310G>T(p.Ala104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CCL24
NM_002991.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.450

Variant links:

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]

CCL24 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045799166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL24	NM_002991.3 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 3 of 3	ENST00000222902.7	NP_002982.2	O00175
CCL24	NM_001371193.1 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 4 of 4		NP_001358122.1
CCL24	XM_011516460.3 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 6 of 6		XP_011514762.1	O00175

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL24	ENST00000222902.7 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 3 of 3	1	NM_002991.3	ENSP00000222902.2		O00175
CCL24	ENST00000416943.1 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 4 of 4	1		ENSP00000400533.1		O00175

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151302

Hom.:

Cov.:

show subpopulations

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151302

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310G>T (p.A104S) alteration is located in exon 3 (coding exon 3) of the CCL24 gene. This alteration results from a G to T substitution at nucleotide position 310, causing the alanine (A) at amino acid position 104 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.29

DANN

Benign

0.074

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.21

.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.69

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.47

N;N

REVEL

Benign

0.025

Sift

Benign

0.94

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;B

Vest4

0.012

MutPred

0.21

Gain of phosphorylation at A104 (P = 0.0132);Gain of phosphorylation at A104 (P = 0.0132);

MVP

0.048

MPC

0.15

ClinPred

0.028

GERP RS

-0.95

Varity_R

0.032

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over