chr16-57365437-G-A

Position:

• chr16-57365437-G-A

Variant summary

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

The ENST00000219235.5(CCL22):​c.*1849G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,312 control chromosomes in the GnomAD database, including 60,477 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 0.89 (60435 hom., cov: 32)
  • Exomes 𝑓: 0.94 (42 hom.)
• Consequence: CCL22 ENST00000219235.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL22	NM_002990.5	c.*1849G>A		3_prime_UTR_variant	3/3	ENST00000219235.5	NP_002981.2
CCL22	XM_047434449.1	c.*1849G>A		3_prime_UTR_variant	4/4		XP_047290405.1
CCL22	XM_047434450.1	c.*1849G>A		3_prime_UTR_variant	4/4		XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL22	ENST00000219235.5	c.*1849G>A		3_prime_UTR_variant	3/3	1	NM_002990.5	ENSP00000219235	P1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135243 AN: 152098 Hom.: 60407 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.899

GnomAD4 exome AF: 0.938 AC: 90 AN: 96 Hom.: 42 Cov.: 0 AF XY: 0.931 AC XY: 67 AN XY: 72

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.949

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.889 AC: 135322 AN: 152216 Hom.: 60435 Cov.: 32 AF XY: 0.885 AC XY: 65893 AN XY: 74426

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.901

Alfa AF: 0.912 Hom.: 24526

Bravo AF: 0.876

Asia WGS AF: 0.783 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.54

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: rs121565; hg19: chr16-57399349;