chr16-57359375-G-A

Variant names:

• chr16-57359375-G-A
• rs223816
• NM_002990.5:c.73+486G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002990.5(CCL22):​c.73+486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 151,750 control chromosomes in the GnomAD database, including 40,804 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 0.70 (40804 hom., cov: 30)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL22	NM_002990.5	c.73+486G>A		intron_variant	Intron 1 of 2	ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.112+486G>A		intron_variant	Intron 2 of 3		XP_047290405.1
CCL22	XM_047434450.1	c.73+486G>A		intron_variant	Intron 2 of 3		XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL22	ENST00000219235.5	c.73+486G>A		intron_variant	Intron 1 of 2	1	NM_002990.5	ENSP00000219235.4

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106227 AN: 151632 Hom.: 40792 Cov.: 30

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.700 AC: 106279 AN: 151750 Hom.: 40804 Cov.: 30 AF XY: 0.698 AC XY: 51785 AN XY: 74198

African (AFR) AF: 0.374 AC: 15459 AN: 41350

American (AMR) AF: 0.694 AC: 10565 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3111 AN: 3464

East Asian (EAS) AF: 0.557 AC: 2879 AN: 5168

South Asian (SAS) AF: 0.699 AC: 3361 AN: 4810

European-Finnish (FIN) AF: 0.861 AC: 9042 AN: 10502

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59433 AN: 67918

Other (OTH) AF: 0.756 AC: 1593 AN: 2106

Alfa AF: 0.788 Hom.: 6194

Bravo AF: 0.674

Asia WGS AF: 0.588 AC: 2044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.17
PhyloP100		-0.24
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: rs223816; hg19: chr16-57393287;