dbSNP rs755346614: CCL20:p.Arg87Gly (chr2-227816374-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004591.3(CCL20):c.259C>G(p.Arg87Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,740 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCL20
NM_004591.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.482

Publications

0 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14430198).

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>G	p.Arg87Gly	missense	Exon 3 of 4	NP_004582.1	P78556-1
	CCL20	NM_001130046.2		c.256C>G	p.Arg86Gly	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>G	p.Arg87Gly	missense	Exon 3 of 4	ENSP00000351671.4	P78556-1
CCL20	ENST00000409189.7	TSL:1	c.256C>G	p.Arg86Gly	missense	Exon 3 of 4	ENSP00000386273.3	P78556-2
CCL20	ENST00000473642.1	TSL:2	n.268C>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1439740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717642

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33036

American (AMR)

AF:

0.00

AC:

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25988

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

85650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53322

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092348

Other (OTH)

AF:

0.0000168

AC:

AN:

59658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.44

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

PhyloP100

0.48

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.055

Sift

Benign

0.31

Sift4G

Benign

0.39

Polyphen

0.31

Vest4

0.30

MutPred

0.50

Loss of solvent accessibility (P = 0.0509)

MVP

0.52

MPC

0.57

ClinPred

0.15

GERP RS

2.2

Varity_R

0.50

gMVP

0.31

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over