rs140681994
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001364905.1(LRBA):c.6214C>T(p.Pro2072Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000696 in 1,608,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.6214C>T | p.Pro2072Ser | missense_variant | 40/57 | ENST00000651943.2 | NP_001351834.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.6214C>T | p.Pro2072Ser | missense_variant | 40/57 | NM_001364905.1 | ENSP00000498582 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 246908Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133468
GnomAD4 exome AF: 0.0000735 AC: 107AN: 1456626Hom.: 0 Cov.: 31 AF XY: 0.0000718 AC XY: 52AN XY: 724348
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74290
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 | May 31, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2083 of the LRBA protein (p.Pro2083Ser). This variant is present in population databases (rs140681994, gnomAD 0.003%). 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: 571369). 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: "Possibly 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