dbSNP rs41398344: CCL22:p.Tyr40His (chr16-57360481-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 13/21 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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.21

Publications

12 publications found

Variant links:

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]

CCL22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 769900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002990.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	NM_002990.5	MANE Select	c.118T>C	p.Tyr40His	missense	Exon 2 of 3	NP_002981.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	ENST00000219235.5	TSL:1 MANE Select	c.118T>C	p.Tyr40His	missense	Exon 2 of 3	ENSP00000219235.4	O00626
	CCL22	ENST00000941195.1		c.118T>C	p.Tyr40His	missense	Exon 3 of 4	ENSP00000611254.1

Frequencies

GnomAD3 genomes

AF:

0.00470

AC:

715

AN:

152234

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00521

AC:

1311

AN:

251462

AF XY:

0.00527

show subpopulations

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 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.:

Cov.:

AF XY:

0.00771

AC XY:

5610

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33480

American (AMR)

AF:

0.00277

AC:

124

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00210

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00519

AC:

448

AN:

86258

European-Finnish (FIN)

AF:

0.00148

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00916

AC:

10181

AN:

1111986

Other (OTH)

AF:

0.00697

AC:

421

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

583

1166

1748

2331

2914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00469

AC:

715

AN:

152352

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

334

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41582

American (AMR)

AF:

0.00503

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00496

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000564

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00773

AC:

526

AN:

68026

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00649

Hom.:

Bravo

AF:

0.00474

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00884

AC:

ExAC

AF:

0.00549

AC:

667

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00900

EpiControl

AF:

0.00753

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.085

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.56

M_CAP

Benign

0.0080

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.99

PhyloP100

1.2

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.039

Sift

Uncertain

0.029

Sift4G

Benign

0.10

Polyphen

0.062

Vest4

0.40

MVP

0.088

MPC

0.76

ClinPred

0.015

GERP RS

3.1

Varity_R

0.23

gMVP

0.86

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over