rs186080

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001364905.1(LRBA):c.4569+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 1,535,700 control chromosomes in the GnomAD database, including 633,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 53770 hom., cov: 30)

Exomes 𝑓: 0.91 ( 580228 hom. )

Consequence

LRBA
NM_001364905.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -0.464

Variant links:

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]

LRBA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-150844091-G-A is Benign according to our data. Variant chr4-150844091-G-A is described in ClinVar as [Benign]. Clinvar id is 196133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150844091-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRBA	NM_001364905.1 linkuse as main transcript	c.4569+9C>T		intron_variant		ENST00000651943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRBA	ENST00000651943.2 linkuse as main transcript	c.4569+9C>T		intron_variant			NM_001364905.1	P3

Frequencies

GnomAD3 genomes

AF:

0.832

AC:

126304

AN:

151876

Hom.:

53747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.951

Gnomad AMR

AF:

0.860

Gnomad ASJ

AF:

0.888

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.846

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.941

Gnomad OTH

AF:

0.858

GnomAD3 exomes

AF:

0.862

AC:

216072

AN:

250696

Hom.:

94363

AF XY:

0.863

AC XY:

116899

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.850

Gnomad ASJ exome

AF:

0.884

Gnomad EAS exome

AF:

0.860

Gnomad SAS exome

AF:

0.730

Gnomad FIN exome

AF:

0.847

Gnomad NFE exome

AF:

0.935

Gnomad OTH exome

AF:

0.891

GnomAD4 exome

AF:

0.913

AC:

1262843

AN:

1383706

Hom.:

580228

Cov.:

AF XY:

0.909

AC XY:

629440

AN XY:

692668

show subpopulations

Gnomad4 AFR exome

AF:

0.618

Gnomad4 AMR exome

AF:

0.848

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

0.878

Gnomad4 SAS exome

AF:

0.737

Gnomad4 FIN exome

AF:

0.852

Gnomad4 NFE exome

AF:

0.945

Gnomad4 OTH exome

AF:

0.891

GnomAD4 genome

AF:

0.831

AC:

126375

AN:

151994

Hom.:

53770

Cov.:

AF XY:

0.826

AC XY:

61358

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.860

Gnomad4 ASJ

AF:

0.888

Gnomad4 EAS

AF:

0.875

Gnomad4 SAS

AF:

0.727

Gnomad4 FIN

AF:

0.846

Gnomad4 NFE

AF:

0.941

Gnomad4 OTH

AF:

0.854

Alfa

AF:

0.918

Hom.:

125382

Bravo

AF:

0.825

Asia WGS

AF:

0.760

AC:

2639

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 10, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Combined immunodeficiency due to LRBA deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

1.0

Dann

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over