19-8056476-A-T

Variant names:

• chr19-8056476-A-T
• rs2032887
• NM_005624.4:c.302A>T

Variant summary

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

The NM_005624.4(CCL25):​c.302A>T​(p.His101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCL25 NM_005624.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 32 publications found

Genes affected

CCL25 (HGNC:10624): (C-C motif chemokine ligand 25) This antimicrobial 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 for dendritic cells, thymocytes, and activated macrophages but is inactive on peripheral blood lymphocytes and neutrophils. The product of this gene binds to chemokine receptor CCR9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

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=0.06309199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL25	NM_005624.4	c.302A>T	p.His101Leu	missense_variant	Exon 4 of 6	ENST00000315626.6	NP_005615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL25	ENST00000315626.6	c.302A>T	p.His101Leu	missense_variant	Exon 4 of 6	2	NM_005624.4	ENSP00000324756.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 15875

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0080
DANN	Benign	0.26
DEOGEN2	Benign	0.22	.;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.18	T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.063	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N;N;.
PhyloP100		-2.2
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.1	D;D;.
REVEL	Benign	0.010
Sift	Benign	0.54	T;T;.
Sift4G	Benign	0.57	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.17
MutPred		0.30		Loss of catalytic residue at K99 (P = 0.0757);Loss of catalytic residue at K99 (P = 0.0757);Loss of catalytic residue at K99 (P = 0.0757);
MVP		0.12
MPC		0.44
ClinPred		0.032	T
GERP RS		-3.0
Varity_R		0.055
gMVP		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2032887; hg19: chr19-8121360;