rs2015070

Positions:

• chr17-36064423-C-T

Variant summary

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

The ENST00000616054.2(CCL18):​c.67+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,607,618 control chromosomes in the GnomAD database, including 9,096 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 0.091 (806 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8290 hom.)
• Consequence: CCL18 ENST00000616054.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL18	NM_002988.4	c.67+14C>T		intron_variant		ENST00000616054.2	NP_002979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL18	ENST00000616054.2	c.67+14C>T		intron_variant		1	NM_002988.4	ENSP00000479955	P1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13833 AN: 152096 Hom.: 796 Cov.: 32

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.119 AC: 29667 AN: 249426 Hom.: 2325 AF XY: 0.116 AC XY: 15652 AN XY: 134854

Gnomad AFR exome AF: 0.0382

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.0984

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0937

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.0998 AC: 145224 AN: 1455404 Hom.: 8290 Cov.: 29 AF XY: 0.101 AC XY: 72801 AN XY: 724370

Gnomad4 AFR exome AF: 0.0344

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.0862

Gnomad4 EAS exome AF: 0.0924

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0935

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0911 AC: 13865 AN: 152214 Hom.: 806 Cov.: 32 AF XY: 0.0936 AC XY: 6963 AN XY: 74402

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.0884

Gnomad4 EAS AF: 0.0969

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0939

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0964 Hom.: 254

Bravo AF: 0.0971

Asia WGS AF: 0.122 AC: 422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2015070; hg19: chr17-34391783;