16-57406984-T-C

Variant names:

• chr16-57406984-T-C
• rs223895
• NM_002987.3:c.-60+2148T>C

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+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
• Publications: 17 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=-0.9).
• 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 rank	MANE	Protein	UniProt
CCL17	NM_002987.3	c.-60+2148T>C		intron_variant	Intron 1 of 3	ENST00000219244.9	NP_002978.1
CCL17	XM_017023530.2	c.25+2148T>C		intron_variant	Intron 3 of 5		XP_016879019.1
CCL17	XM_011523256.3	c.25+2148T>C		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+2148T>C		intron_variant	Intron 1 of 3	1	NM_002987.3	ENSP00000219244.4

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

African (AFR) AF: 0.695 AC: 28769 AN: 41420

American (AMR) AF: 0.543 AC: 8282 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2353 AN: 3466

East Asian (EAS) AF: 0.531 AC: 2734 AN: 5150

South Asian (SAS) AF: 0.474 AC: 2282 AN: 4812

European-Finnish (FIN) AF: 0.582 AC: 6119 AN: 10512

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44930 AN: 67944

Other (OTH) AF: 0.652 AC: 1375 AN: 2110

Alfa AF: 0.652 Hom.: 54394

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
PhyloP100		0.21
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: rs223895; hg19: chr16-57440896;