dbSNP rs2015086: CCL18:c.-86A>G (chr17-36064257-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002988.4(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
NM_002988.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.923

Publications

27 publications found

Variant links:

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]

CCL18 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL18	NM_002988.4 link	c.-86A>G		upstream_gene_variant		ENST00000616054.2	NP_002979.1	P55774

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL18	ENST00000616054.2 link	c.-86A>G		upstream_gene_variant		1	NM_002988.4	ENSP00000479955.1		P55774

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33400

AN:

152002

Hom.:

4671

Cov.:

show subpopulations

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.:

AF XY:

0.157

AC XY:

69153

AN XY:

440174

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

5958

11916

17873

23831

29789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1718

3436

5154

6872

8590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33493

AN:

152120

Hom.:

4702

Cov.:

AF XY:

0.223

AC XY:

16576

AN XY:

74370

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9133

AN:

67996

Other (OTH)

AF:

0.216

AC:

456

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1204

2408

3613

4817

6021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.77

PhyloP100

-0.92

PromoterAI

0.0070

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over