4-150905904-G-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001364905.1(LRBA):c.1689C>A(p.Pro563=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000729 in 1,613,562 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0041 ( 7 hom., cov: 31)
Exomes 𝑓: 0.00038 ( 3 hom. )
Consequence
LRBA
NM_001364905.1 synonymous
NM_001364905.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.17
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 Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 4-150905904-G-T is Benign according to our data. Variant chr4-150905904-G-T is described in ClinVar as [Benign]. Clinvar id is 540404.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-150905904-G-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.17 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00412 (627/152240) while in subpopulation AFR AF= 0.0144 (600/41538). AF 95% confidence interval is 0.0135. There are 7 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.1689C>A | p.Pro563= | synonymous_variant | 13/57 | ENST00000651943.2 | NP_001351834.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.1689C>A | p.Pro563= | synonymous_variant | 13/57 | NM_001364905.1 | ENSP00000498582 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00415 AC: 631AN: 152122Hom.: 7 Cov.: 31
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GnomAD3 exomes AF: 0.00104 AC: 261AN: 250950Hom.: 2 AF XY: 0.000708 AC XY: 96AN XY: 135616
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GnomAD4 exome AF: 0.000376 AC: 550AN: 1461322Hom.: 3 Cov.: 30 AF XY: 0.000316 AC XY: 230AN XY: 726972
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GnomAD4 genome AF: 0.00412 AC: 627AN: 152240Hom.: 7 Cov.: 31 AF XY: 0.00383 AC XY: 285AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
LRBA-related disorder Benign:1
Benign, no assertion criteria provided | 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