17-34287653-A-C

Position:

• chr17-34287653-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000305869.4(CCL11):​c.257A>C​(p.Lys86Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,613,884 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (40 hom.)
• Consequence: CCL11 ENST00000305869.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.91

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037260652).
• BP6: Variant 17-34287653-A-C is Benign according to our data. Variant chr17-34287653-A-C is described in ClinVar as [Benign]. Clinvar id is 777159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0151 (2294/152130) while in subpopulation AFR AF= 0.0492 (2041/41486). AF 95% confidence interval is 0.0474. There are 56 homozygotes in gnomad4. There are 1128 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL11	NM_002986.3	c.257A>C	p.Lys86Thr	missense_variant	3/3	ENST00000305869.4	NP_002977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL11	ENST00000305869.4	c.257A>C	p.Lys86Thr	missense_variant	3/3	1	NM_002986.3	ENSP00000302234	P1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2290 AN: 152014 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00405 AC: 1017 AN: 251332 Hom.: 20 AF XY: 0.00311 AC XY: 422 AN XY: 135848

Gnomad AFR exome AF: 0.0486

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00173 AC: 2529 AN: 1461754 Hom.: 40 Cov.: 30 AF XY: 0.00156 AC XY: 1137 AN XY: 727184

Gnomad4 AFR exome AF: 0.0495

Gnomad4 AMR exome AF: 0.00490

Gnomad4 ASJ exome AF: 0.000497

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000332

Gnomad4 OTH exome AF: 0.00402

GnomAD4 genome AF: 0.0151 AC: 2294 AN: 152130 Hom.: 56 Cov.: 32 AF XY: 0.0152 AC XY: 1128 AN XY: 74376

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00315 Hom.: 19

Bravo AF: 0.0174

ESP6500AA AF: 0.0427 AC: 188

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00467 AC: 567

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.066
Sift	Benign	0.18	T
Sift4G	Benign	0.12	T
Polyphen		0.31	B
Vest4		0.23
MVP		0.65
MPC		0.011
ClinPred		0.049	T
GERP RS		4.0
Varity_R		0.24
gMVP		0.50

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: rs34262946; hg19: chr17-32614672;