rs2074543

chr16-57358904-C-Achr16-57358904-C-G

Variant summary

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

The NM_002990.5(CCL22):c.73+15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,605,500 control chromosomes in the GnomAD database, including 2,211 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 0.026 (176 hom., cov: 32)
  • Exomes 𝑓: 0.023 (2035 hom.)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL22	NM_002990.5	c.73+15C>A		intron_variant		ENST00000219235.5
CCL22	XM_047434449.1	c.112+15C>A		intron_variant
CCL22	XM_047434450.1	c.73+15C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL22	ENST00000219235.5	c.73+15C>A		intron_variant		1	NM_002990.5	P1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3923 AN: 152192 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0325

GnomAD3 exomes AF: 0.0396 AC: 9955 AN: 251084 Hom.: 581 AF XY: 0.0370 AC XY: 5027 AN XY: 135706

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0708

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.219

Gnomad SAS exome AF: 0.0169

Gnomad FIN exome AF: 0.0349

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0365

GnomAD4 exome AF: 0.0234 AC: 33993 AN: 1453190 Hom.: 2035 Cov.: 30 AF XY: 0.0233 AC XY: 16829 AN XY: 723422

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.00913

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.0180

Gnomad4 FIN exome AF: 0.0321

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0257 AC: 3920 AN: 152310 Hom.: 176 Cov.: 32 AF XY: 0.0279 AC XY: 2080 AN XY: 74472

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0103 Hom.: 7

Bravo AF: 0.0291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.092
Dann	Benign	0.69

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: rs2074543; hg19: chr16-57392816; COSMIC: COSV54660539;