rs2015086

Positions:

• chr17-36064257-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 17-36064257-A-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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL18	NM_002988.4			upstream_gene_variant		ENST00000616054.2	NP_002979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL18	ENST00000616054.2			upstream_gene_variant		1	NM_002988.4	ENSP00000479955	P1

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

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.168

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

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.216

Alfa AF: 0.181 Hom.: 479

Bravo AF: 0.233

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2015086; hg19: chr17-34391617;