rs757105953
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001364905.1(LRBA):c.7464G>A(p.Met2488Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,596,582 control chromosomes in the GnomAD database, including 1 homozygotes. 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. M2488L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.7464G>A | p.Met2488Ile | missense_variant | 50/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.7464G>A | p.Met2488Ile | missense_variant | 50/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151990Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000430 AC: 10AN: 232472Hom.: 0 AF XY: 0.0000633 AC XY: 8AN XY: 126372
GnomAD4 exome AF: 0.0000256 AC: 37AN: 1444592Hom.: 1 Cov.: 31 AF XY: 0.0000431 AC XY: 31AN XY: 718712
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151990Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74216
ClinVar
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 30, 2018 | This variant is present in population databases (rs757105953, ExAC 0.03%). This sequence change replaces methionine with isoleucine at codon 2499 of the LRBA protein (p.Met2499Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. This variant has not been reported in the literature in individuals with LRBA-related disease. 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