NM_001371938.1:c.80G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371938.1(CCL26):​c.80G>A​(p.Ser27Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S27I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CCL26
NM_001371938.1 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.219
Variant links:
Genes affected
CCL26 (HGNC:10625): (C-C motif chemokine ligand 26) This gene is one of two Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 7. 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 normal peripheral blood eosinophils and basophils. This protein also has antimicrobial activity, displaying an antibacterial effect on S. pneumoniae, S. aureus, Non-typeable H. influenzae, and P. aeruginosa. The product of this gene is one of three related chemokines that specifically activate chemokine receptor CCR3. This chemokine may contribute to the eosinophil accumulation in atopic diseases. [provided by RefSeq, Jul 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09777588).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCL26NM_001371938.1 linkc.80G>A p.Ser27Asn missense_variant Exon 2 of 3 ENST00000005180.9 NP_001358867.1
CCL26NM_001371936.1 linkc.80G>A p.Ser27Asn missense_variant Exon 3 of 4 NP_001358865.1
CCL26NM_006072.4 linkc.80G>A p.Ser27Asn missense_variant Exon 3 of 4 NP_006063.1 Q9Y258

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCL26ENST00000005180.9 linkc.80G>A p.Ser27Asn missense_variant Exon 2 of 3 1 NM_001371938.1 ENSP00000005180.4 Q9Y258
CCL26ENST00000394905.2 linkc.80G>A p.Ser27Asn missense_variant Exon 3 of 4 1 ENSP00000378365.2 Q9Y258

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
7.7
DANN
Benign
0.75
DEOGEN2
Benign
0.28
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.35
.;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.098
T;T
MetaSVM
Benign
-0.92
T
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.068
Sift
Benign
0.24
T;T
Sift4G
Benign
0.17
T;T
Polyphen
0.018
B;B
Vest4
0.29
MutPred
0.49
Loss of disorder (P = 0.0775);Loss of disorder (P = 0.0775);
MVP
0.061
MPC
0.11
ClinPred
0.17
T
GERP RS
1.7
Varity_R
0.089
gMVP
0.11

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.

Other links and lift over

dbSNP: rs143820988; hg19: chr7-75401315; API