rs371936024
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001364905.1(LRBA):c.499C>T(p.Arg167Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R167S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001364905.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.499C>T | p.Arg167Cys | missense_variant | 4/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.499C>T | p.Arg167Cys | missense_variant | 4/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250948Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135682
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461620Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727096
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 25, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2021 | This sequence change replaces arginine with cysteine at codon 167 of the LRBA protein (p.Arg167Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at