NM_002986.3:c.134G>T

Variant names:

• chr17-34287153-G-T
• NM_002986.3:c.134G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002986.3(CCL11):​c.134G>T​(p.Arg45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCL11 NM_002986.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35181093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL11	NM_002986.3	c.134G>T	p.Arg45Leu	missense_variant	Exon 2 of 3	ENST00000305869.4	NP_002977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL11	ENST00000305869.4	c.134G>T	p.Arg45Leu	missense_variant	Exon 2 of 3	1	NM_002986.3	ENSP00000302234.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461736 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.4
DANN	Benign	0.88
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.049
Sift	Benign	0.11	T
Sift4G	Benign	0.70	T
Polyphen		0.37	B
Vest4		0.24
MutPred		0.64		Loss of methylation at K40 (P = 0.0617);
MVP		0.35
MPC		0.0083
ClinPred		0.36	T
GERP RS		-5.3
Varity_R		0.21
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-32614172;