16-57359309-T-C

Variant names:

• chr16-57359309-T-C
• rs72784897
• NM_002990.5:c.73+420T>C

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+420T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 151,628 control chromosomes in the GnomAD database, including 428 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 0.066 (428 hom., cov: 32)
• Consequence: CCL22 NM_002990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL22	NM_002990.5	c.73+420T>C		intron_variant	Intron 1 of 2	ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.112+420T>C		intron_variant	Intron 2 of 3		XP_047290405.1
CCL22	XM_047434450.1	c.73+420T>C		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+420T>C		intron_variant	Intron 1 of 2	1	NM_002990.5	ENSP00000219235.4

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 9976 AN: 151510 Hom.: 429 Cov.: 32

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0359

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0624

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

GnomAD4 genome AF: 0.0658 AC: 9982 AN: 151628 Hom.: 428 Cov.: 32 AF XY: 0.0676 AC XY: 5013 AN XY: 74146

African (AFR) AF: 0.0614 AC: 2526 AN: 41136

American (AMR) AF: 0.0736 AC: 1125 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1180 AN: 5166

South Asian (SAS) AF: 0.0349 AC: 168 AN: 4814

European-Finnish (FIN) AF: 0.0741 AC: 776 AN: 10470

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0563 AC: 3829 AN: 67988

Other (OTH) AF: 0.0608 AC: 128 AN: 2104

Alfa AF: 0.0535 Hom.: 31

Bravo AF: 0.0690

Asia WGS AF: 0.114 AC: 396 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		0.92
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: rs72784897; hg19: chr16-57393221;