16-57362786-A-G

Variant names:

• chr16-57362786-A-G
• rs223821
• NM_002990.5:c.198-718A>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.198-718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,052 control chromosomes in the GnomAD database, including 67,074 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 0.94 (67074 hom., cov: 29)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL22	NM_002990.5	c.198-718A>G		intron_variant	Intron 2 of 2	ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.237-718A>G		intron_variant	Intron 3 of 3		XP_047290405.1
CCL22	XM_047434450.1	c.198-718A>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.198-718A>G		intron_variant	Intron 2 of 2	1	NM_002990.5	ENSP00000219235.4

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142572 AN: 151934 Hom.: 67018 Cov.: 29

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.938 AC: 142685 AN: 152052 Hom.: 67074 Cov.: 29 AF XY: 0.936 AC XY: 69548 AN XY: 74334

African (AFR) AF: 0.954 AC: 39549 AN: 41438

American (AMR) AF: 0.858 AC: 13090 AN: 15264

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

East Asian (EAS) AF: 0.870 AC: 4487 AN: 5160

South Asian (SAS) AF: 0.903 AC: 4343 AN: 4812

European-Finnish (FIN) AF: 0.953 AC: 10078 AN: 10576

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

European-Non Finnish (NFE) AF: 0.952 AC: 64751 AN: 68016

Other (OTH) AF: 0.947 AC: 1997 AN: 2108

Alfa AF: 0.945 Hom.: 8781

Bravo AF: 0.931

Asia WGS AF: 0.876 AC: 3048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.26
PhyloP100		-1.1
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: rs223821; hg19: chr16-57396698;