4-150265768-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001364905.1(LRBA):āc.8513A>Cā(p.Tyr2838Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001364905.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.8513A>C | p.Tyr2838Ser | missense_variant | 57/57 | ENST00000651943.2 | NP_001351834.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.8513A>C | p.Tyr2838Ser | missense_variant | 57/57 | NM_001364905.1 | ENSP00000498582 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000562 AC: 14AN: 249210Hom.: 0 AF XY: 0.0000741 AC XY: 10AN XY: 134898
GnomAD4 exome AF: 0.000140 AC: 205AN: 1461492Hom.: 0 Cov.: 29 AF XY: 0.000135 AC XY: 98AN XY: 727092
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74312
ClinVar
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 05, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 2849 of the LRBA protein (p.Tyr2849Ser). This variant is present in population databases (rs372010196, gnomAD 0.01%). This missense change has been observed in individual(s) with panuveitis (PMID: 32707200). ClinVar contains an entry for this variant (Variation ID: 652172). 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: "Tolerated"; 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. - |
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Sep 05, 2021 | ACMG classification criteria: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at