rs223900

Positions:

• chr16-57411464-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002987.3(CCL17):​c.-59-2410T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,226 control chromosomes in the GnomAD database, including 45,664 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45664 hom., cov: 33)
• Consequence: CCL17 NM_002987.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

Genes affected

CCL17 (HGNC:10615): (C-C motif chemokine ligand 17) This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for T lymphocytes, but not monocytes or granulocytes. The product of this gene binds to chemokine receptors CCR4 and CCR8. This chemokine plays important roles in T cell development in thymus as well as in trafficking and activation of mature T cells. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL17	NM_002987.3	c.-59-2410T>C		intron_variant		ENST00000219244.9	NP_002978.1
CCL17	XM_017023530.2	c.26-2407T>C		intron_variant			XP_016879019.1
CCL17	XM_011523256.3	c.26-2410T>C		intron_variant			XP_011521558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL17	ENST00000219244.9	c.-59-2410T>C		intron_variant		1	NM_002987.3	ENSP00000219244.4

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116490 AN: 152108 Hom.: 45616 Cov.: 33

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.773

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.766 AC: 116596 AN: 152226 Hom.: 45664 Cov.: 33 AF XY: 0.754 AC XY: 56151 AN XY: 74422

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.775

Alfa AF: 0.746 Hom.: 19467

Bravo AF: 0.769

Asia WGS AF: 0.600 AC: 2087 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs223900; hg19: chr16-57445376;