16-57406984-T-C

Position:

• chr16-57406984-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.-60+2148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,868 control chromosomes in the GnomAD database, including 31,675 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 0.64 (31675 hom., cov: 30)
• Consequence: CCL17 NM_002987.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL17	NM_002987.3	c.-60+2148T>C		intron_variant		ENST00000219244.9
CCL17	XM_011523256.3	c.25+2148T>C		intron_variant
CCL17	XM_017023530.2	c.25+2148T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL17	ENST00000219244.9	c.-60+2148T>C		intron_variant		1	NM_002987.3	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97446 AN: 151750 Hom.: 31641 Cov.: 30

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.642 AC: 97543 AN: 151868 Hom.: 31675 Cov.: 30 AF XY: 0.631 AC XY: 46816 AN XY: 74176

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.652

Alfa AF: 0.654 Hom.: 43069

Bravo AF: 0.642

Asia WGS AF: 0.503 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.79

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: rs223895; hg19: chr16-57440896;