rs1782360

Positions:

chr4-150852441-G-C

Variant summary

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

The NM_001364905.1(LRBA):c.3269C>G(p.Ala1090Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 1,612,950 control chromosomes in the GnomAD database, including 9,262 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1601 hom., cov: 32)

Exomes 𝑓: 0.080 ( 7661 hom. )

Consequence

LRBA
NM_001364905.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0310

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:

LRBA (HGNC:):

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 (MetaRNN=0.0027665794).

BP6

Variant 4-150852441-G-C is Benign according to our data. Variant chr4-150852441-G-C is described in ClinVar as [Benign]. Clinvar id is 281585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150852441-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRBA	NM_001364905.1 linkuse as main transcript	c.3269C>G	p.Ala1090Gly	missense_variant	23/57	ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2 linkuse as main transcript	c.3269C>G	p.Ala1090Gly	missense_variant	23/57		NM_001364905.1	ENSP00000498582.2		A0A494C1L5

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19079

AN:

151926

Hom.:

1596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0556

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.124

AC:

31064

AN:

250652

Hom.:

2808

AF XY:

0.126

AC XY:

17060

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.0798

Gnomad EAS exome

AF:

0.140

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.0613

Gnomad OTH exome

AF:

0.0997

GnomAD4 exome

AF:

0.0797

AC:

116423

AN:

1460906

Hom.:

7661

Cov.:

AF XY:

0.0843

AC XY:

61252

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.0823

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.0526

Gnomad4 OTH exome

AF:

0.0943

GnomAD4 genome

AF:

0.126

AC:

19110

AN:

152044

Hom.:

1601

Cov.:

AF XY:

0.133

AC XY:

9897

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.0556

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0682

Hom.:

357

Bravo

AF:

0.126

TwinsUK

AF:

0.0491

AC:

182

ALSPAC

AF:

0.0485

AC:

187

ESP6500AA

AF:

0.223

AC:

982

ESP6500EA

AF:

0.0586

AC:

504

ExAC

AF:

0.127

AC:

15447

Asia WGS

AF:

0.228

AC:

792

AN:

3478

EpiCase

AF:

0.0557

EpiControl

AF:

0.0591

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. 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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 15, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2020	- -

Combined immunodeficiency due to LRBA deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.019

.;T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.091

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.034

B;B;.

Vest4

0.078

MPC

0.12

ClinPred

0.0015

GERP RS

1.2

Varity_R

0.043

gMVP

0.18

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