rs14304

Positions:

• chr17-36071135-T-C

Variant summary

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

The NM_002988.4(CCL18):​c.*94T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 734,762 control chromosomes in the GnomAD database, including 197,550 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 0.78 (46795 hom., cov: 33)
  • Exomes 𝑓: 0.72 (150755 hom.)
• Consequence: CCL18 NM_002988.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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 (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL18	NM_002988.4	c.*94T>C		3_prime_UTR_variant	3/3	ENST00000616054.2	NP_002979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL18	ENST00000616054.2	c.*94T>C		3_prime_UTR_variant	3/3	1	NM_002988.4	ENSP00000479955	P1
CCL18	ENST00000616474.1	n.370T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118067 AN: 152104 Hom.: 46731 Cov.: 33

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.778

GnomAD4 exome AF: 0.716 AC: 416948 AN: 582538 Hom.: 150755 Cov.: 7 AF XY: 0.718 AC XY: 221438 AN XY: 308238

Gnomad4 AFR exome AF: 0.941

Gnomad4 AMR exome AF: 0.754

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.732

Gnomad4 NFE exome AF: 0.690

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.776 AC: 118194 AN: 152224 Hom.: 46795 Cov.: 33 AF XY: 0.778 AC XY: 57903 AN XY: 74418

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.781

Alfa AF: 0.719 Hom.: 52589

Bravo AF: 0.784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs14304; hg19: chr17-34398495;