rs658559

Positions:

• chr16-57365726-G-A

Variant summary

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

The NM_002990.5(CCL22):​c.*2138G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,296 control chromosomes in the GnomAD database, including 23,939 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 0.53 (23885 hom., cov: 32)
  • Exomes 𝑓: 0.64 (54 hom.)
• Consequence: CCL22 NM_002990.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL22	NM_002990.5	c.*2138G>A		3_prime_UTR_variant	3/3	ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.*2138G>A		3_prime_UTR_variant	4/4		XP_047290405.1
CCL22	XM_047434450.1	c.*2138G>A		3_prime_UTR_variant	4/4		XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL22	ENST00000219235.5	c.*2138G>A		3_prime_UTR_variant	3/3	1	NM_002990.5	ENSP00000219235	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81292 AN: 151918 Hom.: 23881 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.642 AC: 167 AN: 260 Hom.: 54 Cov.: 0 AF XY: 0.654 AC XY: 123 AN XY: 188

Gnomad4 AMR exome AF: 0.333

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.535 AC: 81321 AN: 152036 Hom.: 23885 Cov.: 32 AF XY: 0.534 AC XY: 39723 AN XY: 74322

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.580

Alfa AF: 0.615 Hom.: 6047

Bravo AF: 0.515

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.32

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: rs658559; hg19: chr16-57399638;