rs140666848
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001364905.1(LRBA):āc.2444A>Gā(p.Asn815Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,563,408 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N815N) has been classified as Likely benign.
Frequency
Consequence
NM_001364905.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.2444A>G | p.Asn815Ser | missense_variant | 20/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.2444A>G | p.Asn815Ser | missense_variant | 20/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00214 AC: 325AN: 152150Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00221 AC: 553AN: 250170Hom.: 2 AF XY: 0.00222 AC XY: 300AN XY: 135282
GnomAD4 exome AF: 0.00237 AC: 3344AN: 1411144Hom.: 7 Cov.: 25 AF XY: 0.00227 AC XY: 1601AN XY: 705364
GnomAD4 genome AF: 0.00213 AC: 324AN: 152264Hom.: 1 Cov.: 32 AF XY: 0.00199 AC XY: 148AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2021 | Identified in two consanguinious LRBA-deficient siblings in the published literature with primary immunodeficiency who also had a homozygous frameshift variant in the LRBA gene that was believed to be the cause of their symptoms (Seidel et al., 2015); Identified in multiple affected relatives in a large pedigree in the published literature with Hirschsprung disease in addition to a relative with functional constipation and multiple unaffected relatives (Sribudiani et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25539626, 29601828) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | LRBA: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 20, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jul 10, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 02, 2015 | - - |
Hirschsprung disease, susceptibility to, 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Erasmus University Medical Center | Nov 18, 2016 | - - |
Combined immunodeficiency due to LRBA deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
LRBA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 19, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at