dbSNP rs2032887: CCL25:p.His101Arg (chr19-8056476-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005624.4(CCL25):c.302A>G(p.His101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,613,704 control chromosomes in the GnomAD database, including 46,101 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4906 hom., cov: 33)

Exomes 𝑓: 0.23 ( 41195 hom. )

Consequence

CCL25
NM_005624.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.19

Publications

32 publications found

Variant links:

Genes affected

CCL25 (HGNC:10624): (C-C motif chemokine ligand 25) This antimicrobial gene belongs to the subfamily of small cytokine CC genes. 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 dendritic cells, thymocytes, and activated macrophages but is inactive on peripheral blood lymphocytes and neutrophils. The product of this gene binds to chemokine receptor CCR9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

CCL25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004403174).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL25	NM_005624.4 link	c.302A>G	p.His101Arg	missense_variant	Exon 4 of 6	ENST00000315626.6	NP_005615.2	O15444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL25	ENST00000315626.6 link	c.302A>G	p.His101Arg	missense_variant	Exon 4 of 6	2	NM_005624.4	ENSP00000324756.6		O15444-1C9JDZ7

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37960

AN:

152036

Hom.:

4889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.254

GnomAD2 exomes

AF:

0.237

AC:

59020

AN:

248944

AF XY:

0.234

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.0970

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.235

AC:

343118

AN:

1461550

Hom.:

41195

Cov.:

AF XY:

0.234

AC XY:

170087

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.256

AC:

8576

AN:

33478

American (AMR)

AF:

0.308

AC:

13749

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

6579

AN:

26128

East Asian (EAS)

AF:

0.122

AC:

4830

AN:

39700

South Asian (SAS)

AF:

0.190

AC:

16359

AN:

86232

European-Finnish (FIN)

AF:

0.285

AC:

15197

AN:

53322

Middle Eastern (MID)

AF:

0.246

AC:

1416

AN:

5756

European-Non Finnish (NFE)

AF:

0.236

AC:

262415

AN:

1111848

Other (OTH)

AF:

0.232

AC:

13997

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

14041

28083

42124

56166

70207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8980

17960

26940

35920

44900

<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:

0.250

AC:

38021

AN:

152154

Hom.:

4906

Cov.:

AF XY:

0.250

AC XY:

18588

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.260

AC:

10792

AN:

41512

American (AMR)

AF:

0.307

AC:

4694

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

860

AN:

3472

East Asian (EAS)

AF:

0.104

AC:

540

AN:

5180

South Asian (SAS)

AF:

0.178

AC:

860

AN:

4826

European-Finnish (FIN)

AF:

0.283

AC:

2994

AN:

10590

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16261

AN:

67974

Other (OTH)

AF:

0.255

AC:

538

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1504

3009

4513

6018

7522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.235

Hom.:

15875

Bravo

AF:

0.254

TwinsUK

AF:

0.234

AC:

868

ALSPAC

AF:

0.234

AC:

900

ESP6500AA

AF:

0.247

AC:

1023

ESP6500EA

AF:

0.243

AC:

2044

ExAC

AF:

0.231

AC:

27992

Asia WGS

AF:

0.162

AC:

562

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0030

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.065

.;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.20

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.46

N;N;.

PhyloP100

-2.2

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.024

Sift

Benign

0.50

T;T;.

Sift4G

Benign

0.35

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.022

MPC

0.44

ClinPred

0.0022

GERP RS

-3.0

Varity_R

0.035

gMVP

0.097

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over