rs151281297

Variant names:

• chr17-34287602-C-A
• rs151281297
• NM_002986.3:c.206C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002986.3(CCL11):​c.206C>A​(p.Ala69Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,613,638 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 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: CCL11 NM_002986.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.743
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055169404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002986.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL11	NM_002986.3	MANE Select	c.206C>A	p.Ala69Asp	missense	Exon 3 of 3	NP_002977.1	Q6I9T4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL11	ENST00000305869.4	TSL:1 MANE Select	c.206C>A	p.Ala69Asp	missense	Exon 3 of 3	ENSP00000302234.3	P51671

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251300 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1461514 Hom.: 0 Cov.: 30 AF XY: 0.0000605 AC XY: 44 AN XY: 727092

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000621 AC: 69 AN: 1111696

Other (OTH) AF: 0.0000331 AC: 2 AN: 60378

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74374

African (AFR) AF: 0.0000241 AC: 1 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000107 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.1
DANN	Benign	0.68
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.027	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.74
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.043
Sift	Benign	0.57	T
Sift4G	Benign	0.36	T
Polyphen		0.0020	B
Vest4		0.12
MVP		0.34
MPC		0.0077
ClinPred		0.018	T
GERP RS		-10
Varity_R		0.41
gMVP		0.37
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs151281297; hg19: chr17-32614621;