chr2-203936854-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_012092.4(ICOS):c.40C>T(p.Arg14Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00135 in 1,610,374 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14H) has been classified as Uncertain significance.
Frequency
Consequence
NM_012092.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ICOS | NM_012092.4 | c.40C>T | p.Arg14Cys | missense_variant | 1/5 | ENST00000316386.11 | |
LOC101927840 | XR_427213.4 | n.314+463G>A | intron_variant, non_coding_transcript_variant | ||||
ICOS | XR_007073112.1 | n.92C>T | non_coding_transcript_exon_variant | 1/6 | |||
ICOS | XM_047444022.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ICOS | ENST00000316386.11 | c.40C>T | p.Arg14Cys | missense_variant | 1/5 | 1 | NM_012092.4 | P2 | |
ICOS | ENST00000435193.1 | c.40C>T | p.Arg14Cys | missense_variant | 1/4 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00732 AC: 1113AN: 151982Hom.: 15 Cov.: 32
GnomAD3 exomes AF: 0.00194 AC: 488AN: 250972Hom.: 4 AF XY: 0.00148 AC XY: 201AN XY: 135712
GnomAD4 exome AF: 0.000726 AC: 1059AN: 1458272Hom.: 13 Cov.: 29 AF XY: 0.000620 AC XY: 450AN XY: 725690
GnomAD4 genome ? AF: 0.00732 AC: 1114AN: 152102Hom.: 15 Cov.: 32 AF XY: 0.00683 AC XY: 508AN XY: 74340
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
ICOS-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 22, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 13, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at