21-44230071-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_015259.6(ICOSLG):c.881C>T(p.Pro294Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P294P) has been classified as Likely benign.
Frequency
Consequence
NM_015259.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ICOSLG | NM_015259.6 | c.881C>T | p.Pro294Leu | missense_variant | 6/7 | ENST00000407780.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ICOSLG | ENST00000407780.8 | c.881C>T | p.Pro294Leu | missense_variant | 6/7 | 1 | NM_015259.6 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 74826Hom.: 0 Cov.: 9 FAILED QC
GnomAD3 exomes AF: 0.000485 AC: 75AN: 154564Hom.: 0 AF XY: 0.000561 AC XY: 46AN XY: 82048
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000258 AC: 18AN: 698574Hom.: 2 Cov.: 6 AF XY: 0.0000318 AC XY: 11AN XY: 345910
GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 74880Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0AN XY: 36354
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.881C>T (p.P294L) alteration is located in exon 6 (coding exon 6) of the ICOSLG gene. This alteration results from a C to T substitution at nucleotide position 881, causing the proline (P) at amino acid position 294 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at