rs4784805

Variant names:

• chr16-57407495-C-A
• rs4784805
• NM_002987.3:c.-60+2659C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002987.3(CCL17):​c.-60+2659C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 152,228 control chromosomes in the GnomAD database, including 82 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 0.027 (82 hom., cov: 32)
• Consequence: CCL17 NM_002987.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL17	NM_002987.3	c.-60+2659C>A		intron_variant	Intron 1 of 3	ENST00000219244.9	NP_002978.1
CCL17	XM_017023530.2	c.25+2659C>A		intron_variant	Intron 3 of 5		XP_016879019.1
CCL17	XM_011523256.3	c.25+2659C>A		intron_variant	Intron 3 of 5		XP_011521558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL17	ENST00000219244.9	c.-60+2659C>A		intron_variant	Intron 1 of 3	1	NM_002987.3	ENSP00000219244.4

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4127 AN: 152110 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.00819

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0271 AC: 4130 AN: 152228 Hom.: 82 Cov.: 32 AF XY: 0.0306 AC XY: 2278 AN XY: 74430

African (AFR) AF: 0.00816 AC: 339 AN: 41524

American (AMR) AF: 0.0464 AC: 709 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.0838 AC: 434 AN: 5180

South Asian (SAS) AF: 0.0875 AC: 422 AN: 4822

European-Finnish (FIN) AF: 0.0441 AC: 468 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1636 AN: 68012

Other (OTH) AF: 0.0265 AC: 56 AN: 2110

Alfa AF: 0.0244 Hom.: 106

Bravo AF: 0.0239

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.34
PhyloP100		-0.37
Mutation Taster		=100/0	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: rs4784805; hg19: chr16-57441407;