16-57359309-T-C

Position:

• chr16-57359309-T-C

Variant summary

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

The ENST00000219235.5(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 ENST00000219235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915

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=-0.92).
• 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/exons	MANE	Protein	UniProt
CCL22	NM_002990.5	c.73+420T>C		intron_variant		ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.112+420T>C		intron_variant			XP_047290405.1
CCL22	XM_047434450.1	c.73+420T>C		intron_variant			XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL22	ENST00000219235.5	c.73+420T>C		intron_variant		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

Gnomad4 AFR AF: 0.0614

Gnomad4 AMR AF: 0.0736

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0349

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.0563

Gnomad4 OTH AF: 0.0608

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

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: rs72784897; hg19: chr16-57393221;