rs199469662
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001364905.1(LRBA):c.5047C>T(p.Arg1683Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,826 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001364905.1 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.5047C>T | p.Arg1683Ter | stop_gained | 30/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.5047C>T | p.Arg1683Ter | stop_gained | 30/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152204Hom.: 0 Cov.: 32 FAILED QC
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727210
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 35456). This premature translational stop signal has been observed in individual(s) with LRBA deficiency (PMID: 22608502). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1683*) in the LRBA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LRBA are known to be pathogenic (PMID: 26206937, 26768763). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 08, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at