rs73557194

Positions:

• chr16-57361878-A-G
• chr16-57361878-A-T

Variant summary

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

The NM_002990.5(CCL22):​c.197+1318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 152,276 control chromosomes in the GnomAD database, including 229 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 0.038 (229 hom., cov: 32)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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=-0.84).
• 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.197+1318A>G		intron_variant		ENST00000219235.5
CCL22	XM_047434449.1	c.236+1318A>G		intron_variant
CCL22	XM_047434450.1	c.197+1318A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL22	ENST00000219235.5	c.197+1318A>G		intron_variant		1	NM_002990.5	P1

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5750 AN: 152158 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0378 AC: 5749 AN: 152276 Hom.: 229 Cov.: 32 AF XY: 0.0390 AC XY: 2906 AN XY: 74454

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.0539

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0219

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0224 Hom.: 18

Bravo AF: 0.0432

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.63

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: rs73557194; hg19: chr16-57395790;