Genetic Variant CCL20:p.Arg87Cys (chr2-227816374-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004591.3(CCL20):c.259C>T(p.Arg87Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000942 in 1,591,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CCL20
NM_004591.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.482

Publications

2 publications found

Variant links:

Genes affected

CCL20 (HGNC:10619): (C-C motif chemokine ligand 20) This antimicrobial gene belongs to the subfamily of small cytokine CC genes. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The protein encoded by this gene displays chemotactic activity for lymphocytes and can repress proliferation of myeloid progenitors. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

CCL20 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29954103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004591.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL20	NM_004591.3	MANE Select	c.259C>T	p.Arg87Cys	missense	Exon 3 of 4	NP_004582.1	P78556-1
	CCL20	NM_001130046.2		c.256C>T	p.Arg86Cys	missense	Exon 3 of 4	NP_001123518.1	P78556-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCL20	ENST00000358813.5	TSL:1 MANE Select	c.259C>T	p.Arg87Cys	missense	Exon 3 of 4	ENSP00000351671.4	P78556-1
CCL20	ENST00000409189.7	TSL:1	c.256C>T	p.Arg86Cys	missense	Exon 3 of 4	ENSP00000386273.3	P78556-2
CCL20	ENST00000473642.1	TSL:2	n.268C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249374

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000695

AC:

AN:

1439734

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33036

American (AMR)

AF:

0.0000225

AC:

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25988

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

85648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00000549

AC:

AN:

1092344

Other (OTH)

AF:

0.0000335

AC:

AN:

59658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000329

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.000131

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.61

M_CAP

Benign

0.020

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

PhyloP100

0.48

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.047

Sift

Benign

0.086

Sift4G

Uncertain

0.058

Polyphen

0.99

Vest4

0.33

MutPred

0.49

Gain of catalytic residue at L88 (P = 0.0081)

MVP

0.58

MPC

1.0

ClinPred

0.71

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.30

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over