chr17-34285875-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002986.3(CCL11):​c.67G>A​(p.Ala23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,607,948 control chromosomes in the GnomAD database, including 23,606 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A23V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.15 (1794 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21812 hom.)
• Consequence: CCL11 NM_002986.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.241
• Publications: 64 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023789406).
• BP6: Variant 17-34285875-G-A is Benign according to our data. Variant chr17-34285875-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059737.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

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.67G>A	p.Ala23Thr	missense	Exon 1 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.67G>A	p.Ala23Thr	missense	Exon 1 of 3	ENSP00000302234.3	P51671

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22767 AN: 152064 Hom.: 1795 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.165

GnomAD2 exomes AF: 0.164 AC: 40378 AN: 246160 AF XY: 0.167

Gnomad AFR exome AF: 0.0884

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.174

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.171 AC: 249202 AN: 1455766 Hom.: 21812 Cov.: 30 AF XY: 0.172 AC XY: 124393 AN XY: 724308

African (AFR) AF: 0.0886 AC: 2948 AN: 33266

American (AMR) AF: 0.133 AC: 5870 AN: 44262

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5579 AN: 26046

East Asian (EAS) AF: 0.146 AC: 5743 AN: 39280

South Asian (SAS) AF: 0.155 AC: 13312 AN: 85712

European-Finnish (FIN) AF: 0.166 AC: 8799 AN: 52934

Middle Eastern (MID) AF: 0.195 AC: 1122 AN: 5744

European-Non Finnish (NFE) AF: 0.176 AC: 195119 AN: 1108342

Other (OTH) AF: 0.178 AC: 10710 AN: 60180

GnomAD4 genome AF: 0.150 AC: 22757 AN: 152182 Hom.: 1794 Cov.: 32 AF XY: 0.150 AC XY: 11160 AN XY: 74408

African (AFR) AF: 0.0913 AC: 3791 AN: 41522

American (AMR) AF: 0.146 AC: 2227 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3468

East Asian (EAS) AF: 0.182 AC: 939 AN: 5168

South Asian (SAS) AF: 0.156 AC: 751 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1742 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12055 AN: 68006

Other (OTH) AF: 0.163 AC: 345 AN: 2116

Alfa AF: 0.173 Hom.: 769

Bravo AF: 0.146

TwinsUK AF: 0.160 AC: 592

ALSPAC AF: 0.178 AC: 687

ESP6500AA AF: 0.0935 AC: 412

ESP6500EA AF: 0.178 AC: 1535

ExAC AF: 0.163 AC: 19820

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CCL11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.81
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.90	T
PhyloP100		0.24
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.061
Sift	Benign	0.12	T
Sift4G	Benign	0.16	T
Polyphen		0.43	B
Vest4		0.033
MPC		0.010
ClinPred		0.015	T
GERP RS		-1.5
PromoterAI		-0.020	Neutral
Varity_R		0.079
gMVP		0.49
Mutation Taster		=96/4	polymorphism (auto)

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: rs1129844; hg19: chr17-32612894; COSMIC: COSV59924883;