Genetic Variant NM_002988.4:c.67+14C>T (chr17-36064423-C-T) – 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.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
NM_002988.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.485

Publications

19 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 (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL18	NM_002988.4 link	c.67+14C>T		intron_variant	Intron 1 of 2	ENST00000616054.2	NP_002979.1	P55774

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL18	ENST00000616054.2 link	c.67+14C>T		intron_variant	Intron 1 of 2	1	NM_002988.4	ENSP00000479955.1		P55774

Frequencies

GnomAD3 genomes

AF:

0.0909

AC:

13833

AN:

152096

Hom.:

796

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.119

AC:

29667

AN:

249426

AF XY:

0.116

show subpopulations

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 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.:

AF XY:

0.101

AC XY:

72801

AN XY:

724370

show subpopulations

African (AFR)

AF:

0.0344

AC:

1149

AN:

33354

American (AMR)

AF:

0.249

AC:

11044

AN:

44412

Ashkenazi Jewish (ASJ)

AF:

0.0862

AC:

2248

AN:

26066

East Asian (EAS)

AF:

0.0924

AC:

3659

AN:

39604

South Asian (SAS)

AF:

0.135

AC:

11637

AN:

85952

European-Finnish (FIN)

AF:

0.102

AC:

5433

AN:

53330

Middle Eastern (MID)

AF:

0.0878

AC:

505

AN:

5752

European-Non Finnish (NFE)

AF:

0.0935

AC:

103534

AN:

1106756

Other (OTH)

AF:

0.100

AC:

6015

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

5912

11824

17736

23648

29560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3900

7800

11700

15600

19500

<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:

0.0911

AC:

13865

AN:

152214

Hom.:

806

Cov.:

AF XY:

0.0936

AC XY:

6963

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0394

AC:

1637

AN:

41584

American (AMR)

AF:

0.196

AC:

2987

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0884

AC:

307

AN:

3472

East Asian (EAS)

AF:

0.0969

AC:

501

AN:

5170

South Asian (SAS)

AF:

0.134

AC:

648

AN:

4820

European-Finnish (FIN)

AF:

0.102

AC:

1081

AN:

10600

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0939

AC:

6383

AN:

67988

Other (OTH)

AF:

0.110

AC:

232

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

619

1238

1857

2476

3095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0981

Hom.:

499

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

(source)

DANN

Benign

0.69

PhyloP100

-0.48

PromoterAI

0.054

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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