17-34285875-G-T

Variant names:

• chr17-34285875-G-T
• rs1129844
• NM_002986.3:c.67G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002986.3(CCL11):​c.67G>T​(p.Ala23Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A23T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCL11 NM_002986.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

Genes affected

CCL11 (HGNC:10610): (C-C motif chemokine ligand 11) This antimicrobial gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, displays chemotactic activity for eosinophils, but not mononuclear cells or neutrophils. This eosinophil-specific chemokine is thought to be involved in eosinophilic inflammatory diseases such as atopic dermatitis, allergic rhinitis, asthma and parasitic infections. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18888411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL11	NM_002986.3	c.67G>T	p.Ala23Ser	missense_variant	Exon 1 of 3	ENST00000305869.4	NP_002977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL11	ENST00000305869.4	c.67G>T	p.Ala23Ser	missense_variant	Exon 1 of 3	1	NM_002986.3	ENSP00000302234.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.0
DANN	Benign	0.94
DEOGEN2	Uncertain	0.62	D
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.13
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.91	P
Vest4		0.12
MutPred		0.29		Gain of glycosylation at A23 (P = 0.0016);
MVP		0.39
MPC		0.017
ClinPred		0.39	T
GERP RS		-1.5
Varity_R		0.074
gMVP		0.48

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: rs1129844; hg19: chr17-32612894;