chr21-44229035-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_015259.6(ICOSLG):c.908G>C(p.Ter303SerextTer59) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 0)
Consequence
ICOSLG
NM_015259.6 stop_lost
NM_015259.6 stop_lost
Scores
1
6
Clinical Significance
Conservation
PhyloP100: 1.51
Genes affected
ICOSLG (HGNC:17087): (inducible T cell costimulator ligand) Enables identical protein binding activity. Predicted to be involved in T cell receptor signaling pathway and positive regulation of interleukin-4 production. Located in cytoplasmic ribonucleoprotein granule and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_addAF=-0.699297).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ICOSLG | NM_015259.6 | c.908G>C | p.Ter303SerextTer59 | stop_lost | 7/7 | ENST00000407780.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ICOSLG | ENST00000407780.8 | c.908G>C | p.Ter303SerextTer59 | stop_lost | 7/7 | 1 | NM_015259.6 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
Cov.:
0
GnomAD3 exomes AF: 0.0000725 AC: 18AN: 248140Hom.: 0 AF XY: 0.0000964 AC XY: 13AN XY: 134918
GnomAD3 exomes
AF:
AC:
18
AN:
248140
Hom.:
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AC XY:
13
AN XY:
134918
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GnomAD4 exome Cov.: 4
GnomAD4 exome
Cov.:
4
GnomAD4 genome ? Cov.: 0
GnomAD4 genome
?
Cov.:
0
ExAC
?
AF:
AC:
8
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change disrupts the translational stop signal of the ICOSLG mRNA. It is expected to extend the length of the ICOSLG protein by 59 additional amino acid residues. This variant is present in population databases (rs746057000, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ICOSLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 1392572). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
N;N;N;N
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at