2-227815529-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004591.3(CCL20):c.152G>A(p.Arg51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,458,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CCL20
NM_004591.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.383

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04306975).

BP6

Variant 2-227815529-G-A is Benign according to our data. Variant chr2-227815529-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2376820.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL20	NM_004591.3 linkuse as main transcript	c.152G>A	p.Arg51Gln	missense_variant	2/4	ENST00000358813.5
CCL20	NM_001130046.2 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL20	ENST00000358813.5 linkuse as main transcript	c.152G>A	p.Arg51Gln	missense_variant	2/4	1	NM_004591.3	P4	P78556-1
CCL20	ENST00000409189.7 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/4	1		A1	P78556-2
CCL20	ENST00000473642.1 linkuse as main transcript	n.161G>A		non_coding_transcript_exon_variant	1/3	2
CCL20	ENST00000489160.1 linkuse as main transcript	n.218G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

249948

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1458298

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000991

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000849

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.79

Cadd

Benign

1.1

Dann

Benign

0.86

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.011

Sift

Benign

0.85

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0030

B;B

Vest4

0.21

MVP

0.30

MPC

0.32

ClinPred

0.059

GERP RS

-0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over