NM_002990.5:c.197+390C>T

Variant names:

• chr16-57360950-C-T
• rs223819
• NM_002990.5:c.197+390C>T

Variant summary

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

The NM_002990.5(CCL22):​c.197+390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 151,874 control chromosomes in the GnomAD database, including 48,354 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 (48354 hom., cov: 30)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 12 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL22	NM_002990.5	c.197+390C>T		intron_variant	Intron 2 of 2	ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.236+390C>T		intron_variant	Intron 3 of 3		XP_047290405.1
CCL22	XM_047434450.1	c.197+390C>T		intron_variant	Intron 3 of 3		XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL22	ENST00000219235.5	c.197+390C>T		intron_variant	Intron 2 of 2	1	NM_002990.5	ENSP00000219235.4

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116841 AN: 151756 Hom.: 48345 Cov.: 30

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.770 AC: 116892 AN: 151874 Hom.: 48354 Cov.: 30 AF XY: 0.768 AC XY: 56996 AN XY: 74220

African (AFR) AF: 0.448 AC: 18492 AN: 41322

American (AMR) AF: 0.767 AC: 11706 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3222 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4059 AN: 5162

South Asian (SAS) AF: 0.731 AC: 3511 AN: 4806

European-Finnish (FIN) AF: 0.934 AC: 9869 AN: 10564

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63323 AN: 67982

Other (OTH) AF: 0.822 AC: 1728 AN: 2102

Alfa AF: 0.876 Hom.: 225695

Bravo AF: 0.746

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		2.0
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: rs223819; hg19: chr16-57394862;