rs4359426

Variant names:

• chr16-57358821-A-C
• rs4359426
• NM_002990.5:c.5A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-57358821-A-C
• chr16-57358821-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002990.5(CCL22):​c.5A>C​(p.Asp2Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,612,532 control chromosomes in the GnomAD database, including 715,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.94 (67192 hom., cov: 32)
  • Exomes 𝑓: 0.94 (648266 hom.)
• Consequence: CCL22 NM_002990.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 51 publications found

Genes affected

CCL22 (HGNC:10621): (C-C motif chemokine ligand 22) This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for monocytes, dendritic cells, natural killer cells and for chronically activated T lymphocytes. It also displays a mild activity for primary activated T lymphocytes and has no chemoattractant activity for neutrophils, eosinophils and resting T lymphocytes. The product of this gene binds to chemokine receptor CCR4. This chemokine may play a role in the trafficking of activated T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology. [provided by RefSeq, Sep 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.390018E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002990.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	NM_002990.5	MANE Select	c.5A>C	p.Asp2Ala	missense	Exon 1 of 3	NP_002981.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	ENST00000219235.5	TSL:1 MANE Select	c.5A>C	p.Asp2Ala	missense	Exon 1 of 3	ENSP00000219235.4

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142817 AN: 152188 Hom.: 67136 Cov.: 32

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.946

GnomAD2 exomes AF: 0.915 AC: 230152 AN: 251418 AF XY: 0.921

Gnomad AFR exome AF: 0.954

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.954

Gnomad EAS exome AF: 0.872

Gnomad FIN exome AF: 0.952

Gnomad NFE exome AF: 0.948

Gnomad OTH exome AF: 0.936

GnomAD4 exome AF: 0.942 AC: 1374844 AN: 1460226 Hom.: 648266 Cov.: 36 AF XY: 0.941 AC XY: 684000 AN XY: 726510

African (AFR) AF: 0.954 AC: 31929 AN: 33456

American (AMR) AF: 0.795 AC: 35537 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 24951 AN: 26130

East Asian (EAS) AF: 0.868 AC: 34425 AN: 39682

South Asian (SAS) AF: 0.906 AC: 78125 AN: 86204

European-Finnish (FIN) AF: 0.949 AC: 50687 AN: 53384

Middle Eastern (MID) AF: 0.927 AC: 5314 AN: 5730

European-Non Finnish (NFE) AF: 0.952 AC: 1056831 AN: 1110588

Other (OTH) AF: 0.945 AC: 57045 AN: 60336

GnomAD4 genome AF: 0.938 AC: 142930 AN: 152306 Hom.: 67192 Cov.: 32 AF XY: 0.936 AC XY: 69676 AN XY: 74464

African (AFR) AF: 0.954 AC: 39669 AN: 41572

American (AMR) AF: 0.858 AC: 13117 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3324 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4505 AN: 5172

South Asian (SAS) AF: 0.903 AC: 4359 AN: 4826

European-Finnish (FIN) AF: 0.953 AC: 10123 AN: 10626

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.952 AC: 64767 AN: 68024

Other (OTH) AF: 0.947 AC: 2001 AN: 2112

Alfa AF: 0.944 Hom.: 309172

Bravo AF: 0.931

TwinsUK AF: 0.951 AC: 3527

ALSPAC AF: 0.949 AC: 3659

ESP6500AA AF: 0.955 AC: 4197

ESP6500EA AF: 0.950 AC: 8173

ExAC AF: 0.920 AC: 111680

Asia WGS AF: 0.876 AC: 3050 AN: 3478

EpiCase AF: 0.953

EpiControl AF: 0.953

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.71
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	9.4e-7	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.034
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.40
ClinPred		0.00030	T
GERP RS		3.5
PromoterAI		0.037	Neutral
Varity_R		0.043
gMVP		0.56
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4359426; hg19: chr16-57392733; COSMIC: COSV99536625;