rs223818

Variant names:

• chr16-57360846-C-G
• rs223818
• NM_002990.5:c.197+286C>G

Variant summary

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

The NM_002990.5(CCL22):​c.197+286C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,168 control chromosomes in the GnomAD database, including 48,988 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (48988 hom., cov: 33)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 12 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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL22	NM_002990.5	c.197+286C>G		intron_variant	Intron 2 of 2	ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.236+286C>G		intron_variant	Intron 3 of 3		XP_047290405.1
CCL22	XM_047434450.1	c.197+286C>G		intron_variant	Intron 3 of 3		XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL22	ENST00000219235.5	c.197+286C>G		intron_variant	Intron 2 of 2	1	NM_002990.5	ENSP00000219235.4

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118197 AN: 152050 Hom.: 48972 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.826

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.777 AC: 118257 AN: 152168 Hom.: 48988 Cov.: 33 AF XY: 0.776 AC XY: 57708 AN XY: 74408

African (AFR) AF: 0.474 AC: 19653 AN: 41474

American (AMR) AF: 0.771 AC: 11776 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3220 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4071 AN: 5176

South Asian (SAS) AF: 0.730 AC: 3521 AN: 4820

European-Finnish (FIN) AF: 0.935 AC: 9919 AN: 10614

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63362 AN: 68014

Other (OTH) AF: 0.828 AC: 1751 AN: 2114

Alfa AF: 0.848 Hom.: 7055

Bravo AF: 0.756

Asia WGS AF: 0.700 AC: 2436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.57
PhyloP100		-0.012
Mutation Taster		=100/0	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: rs223818; hg19: chr16-57394758; COSMIC: COSV54659792;