16-57360481-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002990.5(CCL22):c.118T>C(p.Tyr40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,614,214 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (57 hom.)
• Consequence: CCL22 NM_002990.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005359113).
• BP6: Variant 16-57360481-T-C is Benign according to our data. Variant chr16-57360481-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 769900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL22	NM_002990.5	c.118T>C	p.Tyr40His	missense_variant	2/3	ENST00000219235.5
CCL22	XM_047434449.1	c.157T>C	p.Tyr53His	missense_variant	3/4
CCL22	XM_047434450.1	c.118T>C	p.Tyr40His	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL22	ENST00000219235.5	c.118T>C	p.Tyr40His	missense_variant	2/3	1	NM_002990.5	P1

Frequencies

GnomAD3 genomes AF: 0.00470 AC: 715 AN: 152234 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.000564

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00521 AC: 1311 AN: 251462 Hom.: 7 AF XY: 0.00527 AC XY: 716 AN XY: 135906

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00539

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00840

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00777 AC: 11353 AN: 1461862 Hom.: 57 Cov.: 32 AF XY: 0.00771 AC XY: 5610 AN XY: 727232

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00210

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00519

Gnomad4 FIN exome AF: 0.00148

Gnomad4 NFE exome AF: 0.00916

Gnomad4 OTH exome AF: 0.00697

GnomAD4 genome AF: 0.00469 AC: 715 AN: 152352 Hom.: 4 Cov.: 33 AF XY: 0.00448 AC XY: 334 AN XY: 74496

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00496

Gnomad4 FIN AF: 0.000564

Gnomad4 NFE AF: 0.00773

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00671 Hom.: 10

Bravo AF: 0.00474

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00884 AC: 76

ExAC AF: 0.00549 AC: 667

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00900

EpiControl AF: 0.00753

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.039
Sift	Uncertain	0.029	D
Sift4G	Benign	0.10	T
Polyphen		0.062	B
Vest4		0.40
MVP		0.088
MPC		0.76
ClinPred		0.015	T
GERP RS		3.1
Varity_R		0.23
gMVP		0.86

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: rs41398344; hg19: chr16-57394393;