chr4-151014626-T-TTGTCTTCGCTAGC
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001364905.1(LRBA):c.16_17insGCTAGCGAAGACA(p.Asn6SerfsTer2) variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
LRBA
NM_001364905.1 stop_gained, frameshift
NM_001364905.1 stop_gained, frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.17
Genes affected
LRBA (HGNC:1742): (LPS responsive beige-like anchor protein) The protein encoded by this gene is a member of the WDL-BEACH-WD (WBW) gene family. Its expression is induced in B cells and macrophages by bacterial lipopolysaccharides (LPS). The encoded protein associates with protein kinase A and may be involved in leading intracellular vesicles to activated receptor complexes, which aids in the secretion and/or membrane deposition of immune effector molecules. Defects in this gene are associated with the disorder common variable immunodeficiency-8 with autoimmunity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 59 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-151014626-T-TTGTCTTCGCTAGC is Pathogenic according to our data. Variant chr4-151014626-T-TTGTCTTCGCTAGC is described in ClinVar as [Pathogenic]. Clinvar id is 540378.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.16_17insGCTAGCGAAGACA | p.Asn6SerfsTer2 | stop_gained, frameshift_variant | 2/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.16_17insGCTAGCGAAGACA | p.Asn6SerfsTer2 | stop_gained, frameshift_variant | 2/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LRBA are known to be pathogenic (PMID: 26206937, 26768763). This variant has not been reported in the literature in individuals with LRBA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn6Serfs*2) in the LRBA gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at