Variant 7-75811923-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CCL24
NM_002991.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.944

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:

Genome browser will be placed here

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=0.06647229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCL24	NM_002991.3 linkuse as main transcript	c.233A>G	p.Lys78Arg	missense_variant	3/3	ENST00000222902.7
CCL24	NM_001371193.1 linkuse as main transcript	c.233A>G	p.Lys78Arg	missense_variant	4/4
CCL24	XM_011516460.3 linkuse as main transcript	c.233A>G	p.Lys78Arg	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL24	ENST00000222902.7 linkuse as main transcript	c.233A>G	p.Lys78Arg	missense_variant	3/3	1	NM_002991.3	P1
CCL24	ENST00000416943.1 linkuse as main transcript	c.233A>G	p.Lys78Arg	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148076

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:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461478

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148076

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

71898

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:

0.0000297

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.233A>G (p.K78R) alteration is located in exon 3 (coding exon 3) of the CCL24 gene. This alteration results from a A to G substitution at nucleotide position 233, causing the lysine (K) at amino acid position 78 to be replaced by an arginine (R). 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

0.076

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.0

DANN

Benign

0.93

DEOGEN2

Benign

0.067

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.49

.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.0080

Sift

Benign

0.13

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.010

B;B

Vest4

0.14

MutPred

0.43

Loss of methylation at K78 (P = 0.0112);Loss of methylation at K78 (P = 0.0112);

MVP

0.20

MPC

0.14

ClinPred

0.049

GERP RS

-0.93

Varity_R

0.073

gMVP

0.26

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