rs2015086

Variant names:

• chr17-36064257-A-G
• rs2015086
• NM_002988.4:c.-86A>G

Variant summary

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

The ENST00000616054.2(CCL18):​c.-86A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 985,202 control chromosomes in the GnomAD database, including 16,633 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 0.22 (4702 hom., cov: 32)
  • Exomes 𝑓: 0.16 (11931 hom.)
• Consequence: CCL18 ENST00000616054.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 27 publications found

Genes affected

CCL18 (HGNC:10616): (C-C motif chemokine ligand 18) This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 17. 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 naive T cells, CD4+ and CD8+ T cells and nonactivated lymphocytes, but not for monocytes or granulocytes. This chemokine attracts naive T lymphocytes toward dendritic cells and activated macrophages in lymph nodes. It may play a role in both humoral and cell-mediated immunity responses. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000616054.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL18	NM_002988.4	MANE Select	c.-86A>G		upstream_gene	N/A	NP_002979.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL18	ENST00000616054.2	TSL:1 MANE Select	c.-86A>G		upstream_gene	N/A	ENSP00000479955.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33400 AN: 152002 Hom.: 4671 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.157 AC: 130753 AN: 833082 Hom.: 11931 Cov.: 12 AF XY: 0.157 AC XY: 69153 AN XY: 440174

African (AFR) AF: 0.381 AC: 8060 AN: 21154

American (AMR) AF: 0.285 AC: 12189 AN: 42694

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3273 AN: 22140

East Asian (EAS) AF: 0.103 AC: 3788 AN: 36852

South Asian (SAS) AF: 0.219 AC: 16107 AN: 73412

European-Finnish (FIN) AF: 0.157 AC: 8286 AN: 52792

Middle Eastern (MID) AF: 0.152 AC: 665 AN: 4368

European-Non Finnish (NFE) AF: 0.133 AC: 71731 AN: 539962

Other (OTH) AF: 0.168 AC: 6654 AN: 39708

GnomAD4 genome AF: 0.220 AC: 33493 AN: 152120 Hom.: 4702 Cov.: 32 AF XY: 0.223 AC XY: 16576 AN XY: 74370

African (AFR) AF: 0.383 AC: 15890 AN: 41472

American (AMR) AF: 0.257 AC: 3931 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3466

East Asian (EAS) AF: 0.122 AC: 633 AN: 5182

South Asian (SAS) AF: 0.218 AC: 1051 AN: 4816

European-Finnish (FIN) AF: 0.161 AC: 1711 AN: 10596

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9133 AN: 67996

Other (OTH) AF: 0.216 AC: 456 AN: 2108

Alfa AF: 0.174 Hom.: 767

Bravo AF: 0.233

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.77
PhyloP100		-0.92
PromoterAI		0.0070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2015086; hg19: chr17-34391617;