17-34285875-G-A

Position:

• chr17-34285875-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000305869.4(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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (1794 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21812 hom.)
• Consequence: CCL11 ENST00000305869.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 Benign. Variant got -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 id is 3059737.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-34285875-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL11	NM_002986.3	c.67G>A	p.Ala23Thr	missense_variant	1/3	ENST00000305869.4	NP_002977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL11	ENST00000305869.4	c.67G>A	p.Ala23Thr	missense_variant	1/3	1	NM_002986.3	ENSP00000302234	P1

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

GnomAD3 exomes AF: 0.164 AC: 40378 AN: 246160 Hom.: 3499 AF XY: 0.167 AC XY: 22301 AN XY: 133186

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 SAS exome AF: 0.156

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

Gnomad4 AFR exome AF: 0.0886

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.178

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

Gnomad4 AFR AF: 0.0913

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.163

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CCL11-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	P
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
Varity_R		0.079
gMVP		0.49

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; COSMIC: COSV59924883;