dbSNP rs199918432: CCL25:p.Ile38Val (chr19-8056190-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005624.4(CCL25):c.112A>G(p.Ile38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000919 in 1,556,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I38T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000098 ( 1 hom. )

Consequence

CCL25
NM_005624.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.812

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0704132).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005624.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCL25	NM_005624.4	MANE Select	c.112A>G	p.Ile38Val	missense	Exon 3 of 6	NP_005615.2
CCL25	NM_001394634.1		c.112A>G	p.Ile38Val	missense	Exon 4 of 7	NP_001381563.1	O15444-1
CCL25	NM_001394635.1		c.112A>G	p.Ile38Val	missense	Exon 4 of 7	NP_001381564.1	O15444-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCL25	ENST00000315626.6	TSL:2 MANE Select	c.112A>G	p.Ile38Val	missense	Exon 3 of 6	ENSP00000324756.6	O15444-1
CCL25	ENST00000390669.7	TSL:1	c.112A>G	p.Ile38Val	missense	Exon 2 of 5	ENSP00000375086.3	O15444-1
CCL25	ENST00000680506.1		c.112A>G	p.Ile38Val	missense	Exon 4 of 7	ENSP00000505422.1	O15444-1

Frequencies

GnomAD3 genomes

AF:

0.0000337

AC:

AN:

148564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000739

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000194

AC:

AN:

206466

AF XY:

0.0000271

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000417

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000980

AC:

138

AN:

1408152

Hom.:

Cov.:

AF XY:

0.0000849

AC XY:

AN XY:

694968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31886

American (AMR)

AF:

0.00

AC:

AN:

36684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22482

East Asian (EAS)

AF:

0.00

AC:

AN:

39166

South Asian (SAS)

AF:

0.00

AC:

AN:

77076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5508

European-Non Finnish (NFE)

AF:

0.000125

AC:

136

AN:

1085882

Other (OTH)

AF:

0.0000345

AC:

AN:

57922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000337

AC:

AN:

148564

Hom.:

Cov.:

AF XY:

0.0000416

AC XY:

AN XY:

72056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40296

American (AMR)

AF:

0.00

AC:

AN:

14296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

4988

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000739

AC:

AN:

67652

Other (OTH)

AF:

0.00

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000764

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0020

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.070

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.32

M_CAP

Benign

0.0096

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.81

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.10

REVEL

Benign

0.021

Sift

Benign

0.49

Sift4G

Benign

0.80

Polyphen

0.077

Vest4

0.043

MVP

0.13

MPC

0.31

ClinPred

0.039

GERP RS

-7.3

Varity_R

0.016

gMVP

0.44

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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