rs4359426

chr16-57358821-A-Cchr16-57358821-A-T

Variant summary

Our verdict is Benign. Variant got -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. 11/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL22	NM_002990.5	c.5A>C	p.Asp2Ala	missense_variant	1/3	ENST00000219235.5
CCL22	XM_047434449.1	c.44A>C	p.Asp15Ala	missense_variant	2/4
CCL22	XM_047434450.1	c.5A>C	p.Asp2Ala	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL22	ENST00000219235.5	c.5A>C	p.Asp2Ala	missense_variant	1/3	1	NM_002990.5	P1

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

GnomAD3 exomes AF: 0.915 AC: 230152 AN: 251418 Hom.: 105941 AF XY: 0.921 AC XY: 125117 AN XY: 135880

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 SAS exome AF: 0.904

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

Gnomad4 AFR exome AF: 0.954

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.955

Gnomad4 EAS exome AF: 0.868

Gnomad4 SAS exome AF: 0.906

Gnomad4 FIN exome AF: 0.949

Gnomad4 NFE exome AF: 0.952

Gnomad4 OTH exome AF: 0.945

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

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.957

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.952

Gnomad4 OTH AF: 0.947

Alfa AF: 0.946 Hom.: 151710

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 v4.3

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
MutationTaster	Benign	1.0	P
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
Varity_R		0.043
gMVP		0.56

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

Other links and lift over

dbSNP: rs4359426; hg19: chr16-57392733;