rs150823624

Variant names:

• chr2-227816337-C-G
• rs150823624
• NM_004591.3:c.222C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-227816337-C-G
• chr2-227816337-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004591.3(CCL20):​c.222C>G​(p.Cys74Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C74C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCL20 NM_004591.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.994

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.222C>G	p.Cys74Trp	missense	Exon 3 of 4	NP_004582.1	P78556-1
	CCL20	NM_001130046.2		c.219C>G	p.Cys73Trp	missense	Exon 3 of 4	NP_001123518.1	P78556-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL20	ENST00000358813.5	TSL:1 MANE Select	c.222C>G	p.Cys74Trp	missense	Exon 3 of 4	ENSP00000351671.4	P78556-1
	CCL20	ENST00000409189.7	TSL:1	c.219C>G	p.Cys73Trp	missense	Exon 3 of 4	ENSP00000386273.3	P78556-2
	CCL20	ENST00000473642.1	TSL:2	n.231C>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250468 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.26	D
PhyloP100		-0.70
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-11	D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.95		Gain of MoRF binding (P = 0.0181)
MVP		0.67
MPC		1.1
ClinPred		1.0	D
GERP RS		-3.7
Varity_R		0.99
gMVP		0.87
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150823624; hg19: chr2-228681053;