Variant rs4359426 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002990.5(CCL22):c.5A>C(p.Asp2Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,612,532 control chromosomes in the GnomAD database, including 715,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.94 ( 67192 hom., cov: 32)

Exomes 𝑓: 0.94 ( 648266 hom. )

Consequence

CCL22
NM_002990.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.390018E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL22	NM_002990.5 link	c.5A>C	p.Asp2Ala	missense_variant	1/3	ENST00000219235.5	NP_002981.2	O00626
CCL22	XM_047434449.1 link	c.44A>C	p.Asp15Ala	missense_variant	2/4		XP_047290405.1
CCL22	XM_047434450.1 link	c.5A>C	p.Asp2Ala	missense_variant	2/4		XP_047290406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL22	ENST00000219235.5 link	c.5A>C	p.Asp2Ala	missense_variant	1/3	1	NM_002990.5	ENSP00000219235.4		O00626

Frequencies

GnomAD3 genomes

AF:

0.938

AC:

142817

AN:

152188

Hom.:

67136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.954

Gnomad AMI

AF:

0.862

Gnomad AMR

AF:

0.858

Gnomad ASJ

AF:

0.957

Gnomad EAS

AF:

0.871

Gnomad SAS

AF:

0.904

Gnomad FIN

AF:

0.953

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.952

Gnomad OTH

AF:

0.946

GnomAD3 exomes

AF:

0.915

AC:

230152

AN:

251418

Hom.:

105941

AF XY:

0.921

AC XY:

125117

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.954

Gnomad AMR exome

AF:

0.786

Gnomad ASJ exome

AF:

0.954

Gnomad EAS exome

AF:

0.872

Gnomad SAS exome

AF:

0.904

Gnomad FIN exome

AF:

0.952

Gnomad NFE exome

AF:

0.948

Gnomad OTH exome

AF:

0.936

GnomAD4 exome

AF:

0.942

AC:

1374844

AN:

1460226

Hom.:

648266

Cov.:

AF XY:

0.941

AC XY:

684000

AN XY:

726510

show subpopulations

Gnomad4 AFR exome

AF:

0.954

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.955

Gnomad4 EAS exome

AF:

0.868

Gnomad4 SAS exome

AF:

0.906

Gnomad4 FIN exome

AF:

0.949

Gnomad4 NFE exome

AF:

0.952

Gnomad4 OTH exome

AF:

0.945

GnomAD4 genome

AF:

0.938

AC:

142930

AN:

152306

Hom.:

67192

Cov.:

AF XY:

0.936

AC XY:

69676

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.954

Gnomad4 AMR

AF:

0.858

Gnomad4 ASJ

AF:

0.957

Gnomad4 EAS

AF:

0.871

Gnomad4 SAS

AF:

0.903

Gnomad4 FIN

AF:

0.953

Gnomad4 NFE

AF:

0.952

Gnomad4 OTH

AF:

0.947

Alfa

AF:

0.946

Hom.:

151710

Bravo

AF:

0.931

TwinsUK

AF:

0.951

AC:

3527

ALSPAC

AF:

0.949

AC:

3659

ESP6500AA

AF:

0.955

AC:

4197

ESP6500EA

AF:

0.950

AC:

8173

ExAC

AF:

0.920

AC:

111680

Asia WGS

AF:

0.876

AC:

3050

AN:

3478

EpiCase

AF:

0.953

EpiControl

AF:

0.953

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.15

MetaRNN

Benign

9.4e-7

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.49

PROVEAN

Benign

2.5

REVEL

Benign

0.034

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.028

MPC

0.40

ClinPred

0.00030

GERP RS

3.5

Varity_R

0.043

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over