rs75761402
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001364905.1(LRBA):c.4713G>A(p.Glu1571=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 1,596,616 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0046 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 3 hom. )
Consequence
LRBA
NM_001364905.1 synonymous
NM_001364905.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.396
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 4-150831833-C-T is Benign according to our data. Variant chr4-150831833-C-T is described in ClinVar as [Benign]. Clinvar id is 540414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150831833-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.396 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00458 (697/152242) while in subpopulation AFR AF= 0.016 (666/41522). AF 95% confidence interval is 0.015. There are 6 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.4713G>A | p.Glu1571= | synonymous_variant | 29/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.4713G>A | p.Glu1571= | synonymous_variant | 29/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00461 AC: 701AN: 152124Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00110 AC: 263AN: 240114Hom.: 2 AF XY: 0.000747 AC XY: 97AN XY: 129780
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GnomAD4 exome AF: 0.000421 AC: 608AN: 1444374Hom.: 3 Cov.: 30 AF XY: 0.000357 AC XY: 256AN XY: 717094
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GnomAD4 genome ? AF: 0.00458 AC: 697AN: 152242Hom.: 6 Cov.: 32 AF XY: 0.00431 AC XY: 321AN XY: 74456
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
LRBA-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at