rs143351602
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_001364905.1(LRBA):c.8440C>T(p.Arg2814Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000129 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R2814Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001364905.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.8440C>T | p.Arg2814Trp | missense_variant | 56/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.8440C>T | p.Arg2814Trp | missense_variant | 56/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000598 AC: 91AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251282Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135792
GnomAD4 exome AF: 0.0000800 AC: 117AN: 1461864Hom.: 0 Cov.: 30 AF XY: 0.0000839 AC XY: 61AN XY: 727236
GnomAD4 genome ? AF: 0.000598 AC: 91AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.000511 AC XY: 38AN XY: 74434
ClinVar
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | LRBA NM_006726.4 exon 57 p.Arg2825Trp (c.8473C>T): This variant has not been reported in the literature but is present in 0.1% (45/24964) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/4-151199033-G-A). This variant is present in ClinVar (Variation ID:568471). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2825 of the LRBA protein (p.Arg2825Trp). This variant is present in population databases (rs143351602, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 568471). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 26, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35753512, 34329649) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at