chr16-57361014-C-T

Variant names:

• chr16-57361014-C-T
• rs223820
• NM_002990.5:c.197+454C>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.197+454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 151,976 control chromosomes in the GnomAD database, including 48,357 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 0.77 (48357 hom., cov: 31)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 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.197+454C>T		intron	N/A	NP_002981.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	ENST00000219235.5	TSL:1 MANE Select	c.197+454C>T		intron	N/A	ENSP00000219235.4

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116880 AN: 151858 Hom.: 48348 Cov.: 31

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.769 AC: 116931 AN: 151976 Hom.: 48357 Cov.: 31 AF XY: 0.768 AC XY: 57050 AN XY: 74300

African (AFR) AF: 0.447 AC: 18509 AN: 41386

American (AMR) AF: 0.767 AC: 11719 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3218 AN: 3468

East Asian (EAS) AF: 0.786 AC: 4059 AN: 5162

South Asian (SAS) AF: 0.730 AC: 3512 AN: 4814

European-Finnish (FIN) AF: 0.934 AC: 9897 AN: 10592

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

European-Non Finnish (NFE) AF: 0.931 AC: 63306 AN: 67964

Other (OTH) AF: 0.821 AC: 1729 AN: 2106

Alfa AF: 0.828 Hom.: 6757

Bravo AF: 0.746

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		0.17
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: rs223820; hg19: chr16-57394926;