16-57357856-A-G

Variant names:

• chr16-57357856-A-G
• rs223888
• XM_047434449.1:c.-284A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047434449.1(CCL22):​c.-284A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,234 control chromosomes in the GnomAD database, including 45,315 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 (45315 hom., cov: 33)
• Consequence: CCL22 XM_047434449.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL22	XM_047434449.1	c.-284A>G		upstream_gene_variant			XP_047290405.1
CCL22	XM_047434450.1	c.-107A>G		upstream_gene_variant			XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116981 AN: 152116 Hom.: 45281 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.769 AC: 117068 AN: 152234 Hom.: 45315 Cov.: 33 AF XY: 0.767 AC XY: 57100 AN XY: 74422

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.775

Alfa AF: 0.785 Hom.: 5525

Bravo AF: 0.764

Asia WGS AF: 0.640 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs223888; hg19: chr16-57391768;