Variant 2-227815559-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000358813.5(CCL20):c.182A>G(p.Asn61Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,551,868 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 3 hom. )

Consequence

CCL20
ENST00000358813.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1739394).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL20	NM_004591.3 linkuse as main transcript	c.182A>G	p.Asn61Ser	missense_variant	2/4	ENST00000358813.5	NP_004582.1
CCL20	NM_001130046.2 linkuse as main transcript	c.179A>G	p.Asn60Ser	missense_variant	2/4		NP_001123518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL20	ENST00000358813.5 linkuse as main transcript	c.182A>G	p.Asn61Ser	missense_variant	2/4	1	NM_004591.3	ENSP00000351671	P4	P78556-1
CCL20	ENST00000409189.7 linkuse as main transcript	c.179A>G	p.Asn60Ser	missense_variant	2/4	1		ENSP00000386273	A1	P78556-2
CCL20	ENST00000473642.1 linkuse as main transcript	n.191A>G		non_coding_transcript_exon_variant	1/3	2
CCL20	ENST00000489160.1 linkuse as main transcript	n.248A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000114

AC:

AN:

246368

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

133190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000125

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000101

AC:

142

AN:

1399570

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

699854

show subpopulations

Gnomad4 AFR exome

AF:

0.000311

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000430

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000699

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000874

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000437

EpiControl

AF:

0.000179

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.182A>G (p.N61S) alteration is located in exon 2 (coding exon 2) of the CCL20 gene. This alteration results from a A to G substitution at nucleotide position 182, causing the asparagine (N) at amino acid position 61 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.60

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.063

Sift

Benign

0.040

D;D

Sift4G

Benign

0.30

T;T

Polyphen

0.0020

B;B

Vest4

0.15

MVP

0.46

MPC

0.23

ClinPred

0.099

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.28

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