16-57410664-T-G

Variant names:

• chr16-57410664-T-G
• rs223899
• NM_002987.3:c.-59-3210T>G

Variant summary

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

The NM_002987.3(CCL17):​c.-59-3210T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,180 control chromosomes in the GnomAD database, including 49,765 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 0.80 (49765 hom., cov: 32)
• Consequence: CCL17 NM_002987.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• Publications: 16 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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL17	NM_002987.3	c.-59-3210T>G		intron_variant	Intron 1 of 3	ENST00000219244.9	NP_002978.1
CCL17	XM_017023530.2	c.26-3207T>G		intron_variant	Intron 3 of 5		XP_016879019.1
CCL17	XM_011523256.3	c.26-3210T>G		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.-59-3210T>G		intron_variant	Intron 1 of 3	1	NM_002987.3	ENSP00000219244.4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121845 AN: 152062 Hom.: 49700 Cov.: 32

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.801 AC: 121971 AN: 152180 Hom.: 49765 Cov.: 32 AF XY: 0.793 AC XY: 59016 AN XY: 74390

African (AFR) AF: 0.950 AC: 39463 AN: 41548

American (AMR) AF: 0.677 AC: 10351 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2699 AN: 3472

East Asian (EAS) AF: 0.622 AC: 3210 AN: 5162

South Asian (SAS) AF: 0.696 AC: 3364 AN: 4830

European-Finnish (FIN) AF: 0.713 AC: 7552 AN: 10590

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52696 AN: 67968

Other (OTH) AF: 0.810 AC: 1712 AN: 2114

Alfa AF: 0.770 Hom.: 28420

Bravo AF: 0.803

Asia WGS AF: 0.710 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.93
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: rs223899; hg19: chr16-57444576;