Genetic Variant NM_002988.4:c.*94T>C (chr17-36071135-T-C) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

Publications

23 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=-0.8).

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 rank	MANE	Protein	UniProt
CCL18	NM_002988.4 link	c.*94T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000616054.2	NP_002979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL18	ENST00000616054.2 link	c.*94T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_002988.4	ENSP00000479955.1
CCL18	ENST00000616474.1 link	n.370T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.776

AC:

118067

AN:

152104

Hom.:

46731

Cov.:

show subpopulations

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.:

AF XY:

0.718

AC XY:

221438

AN XY:

308238

show subpopulations

African (AFR)

AF:

0.941

AC:

14066

AN:

14940

American (AMR)

AF:

0.754

AC:

19167

AN:

25404

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

12052

AN:

15308

East Asian (EAS)

AF:

0.666

AC:

22762

AN:

34172

South Asian (SAS)

AF:

0.782

AC:

42397

AN:

54198

European-Finnish (FIN)

AF:

0.732

AC:

35716

AN:

48778

Middle Eastern (MID)

AF:

0.792

AC:

2801

AN:

3538

European-Non Finnish (NFE)

AF:

0.690

AC:

245689

AN:

355864

Other (OTH)

AF:

0.735

AC:

22298

AN:

30336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5921

11841

17762

23682

29603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2388

4776

7164

9552

11940

<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:

0.776

AC:

118194

AN:

152224

Hom.:

46795

Cov.:

AF XY:

0.778

AC XY:

57903

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.939

AC:

39047

AN:

41572

American (AMR)

AF:

0.759

AC:

11614

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.803

AC:

2788

AN:

3470

East Asian (EAS)

AF:

0.669

AC:

3454

AN:

5166

South Asian (SAS)

AF:

0.775

AC:

3744

AN:

4828

European-Finnish (FIN)

AF:

0.744

AC:

7884

AN:

10594

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47167

AN:

67984

Other (OTH)

AF:

0.781

AC:

1647

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1306

2612

3919

5225

6531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.724

Hom.:

72263

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

(source)

PhyloP100

-1.5

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