17-36070248-C-T

Variant names:

• chr17-36070248-C-T
• rs854472
• NM_002988.4:c.68-199C>T

Variant summary

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

The NM_002988.4(CCL18):​c.68-199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 540,750 control chromosomes in the GnomAD database, including 147,415 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 (46675 hom., cov: 31)
  • Exomes 𝑓: 0.72 (100740 hom.)
• Consequence: CCL18 NM_002988.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 1 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=-0.88).
• 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 rank	MANE	Protein	UniProt
CCL18	NM_002988.4	c.68-199C>T		intron_variant	Intron 1 of 2	ENST00000616054.2	NP_002979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL18	ENST00000616054.2	c.68-199C>T		intron_variant	Intron 1 of 2	1	NM_002988.4	ENSP00000479955.1
CCL18	ENST00000616474.1	n.-126C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117897 AN: 152062 Hom.: 46611 Cov.: 31

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.776

GnomAD4 exome AF: 0.717 AC: 278723 AN: 388568 Hom.: 100740 AF XY: 0.721 AC XY: 146315 AN XY: 203014

African (AFR) AF: 0.939 AC: 9778 AN: 10416

American (AMR) AF: 0.760 AC: 11459 AN: 15068

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 9778 AN: 12412

East Asian (EAS) AF: 0.665 AC: 18234 AN: 27406

South Asian (SAS) AF: 0.783 AC: 25865 AN: 33032

European-Finnish (FIN) AF: 0.718 AC: 19699 AN: 27422

Middle Eastern (MID) AF: 0.784 AC: 1405 AN: 1792

European-Non Finnish (NFE) AF: 0.695 AC: 165195 AN: 237704

Other (OTH) AF: 0.742 AC: 17310 AN: 23316

GnomAD4 genome AF: 0.776 AC: 118024 AN: 152182 Hom.: 46675 Cov.: 31 AF XY: 0.777 AC XY: 57778 AN XY: 74372

African (AFR) AF: 0.939 AC: 39024 AN: 41554

American (AMR) AF: 0.759 AC: 11605 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2789 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3453 AN: 5172

South Asian (SAS) AF: 0.777 AC: 3741 AN: 4814

European-Finnish (FIN) AF: 0.735 AC: 7768 AN: 10568

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47150 AN: 67990

Other (OTH) AF: 0.780 AC: 1645 AN: 2110

Alfa AF: 0.741 Hom.: 5235

Bravo AF: 0.784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs854472; hg19: chr17-34397608;