rs2290846

Variant names:

Variant summary

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

The NM_001364905.1(LRBA):c.8393C>T(p.Ser2798Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,782 control chromosomes in the GnomAD database, including 53,568 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3399 hom., cov: 32)

Exomes 𝑓: 0.25 ( 50169 hom. )

Consequence

LRBA
NM_001364905.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.06

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 (MetaRNN=0.0014055073).

BP6

Variant 4-150277928-G-A is Benign according to our data. Variant chr4-150277928-G-A is described in ClinVar as [Benign]. Clinvar id is 403047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1 link	c.8393C>T	p.Ser2798Leu	missense_variant	Exon 56 of 57	ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2 link	c.8393C>T	p.Ser2798Leu	missense_variant	Exon 56 of 57		NM_001364905.1	ENSP00000498582.2		A0A494C1L5

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28233

AN:

151948

Hom.:

3399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0472

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.201

AC:

50509

AN:

251200

Hom.:

6000

AF XY:

0.203

AC XY:

27510

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.0449

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.265

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.254

AC:

370892

AN:

1461716

Hom.:

50169

Cov.:

AF XY:

0.249

AC XY:

181233

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0414

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.282

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.186

AC:

28229

AN:

152066

Hom.:

3399

Cov.:

AF XY:

0.180

AC XY:

13384

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0471

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.247

Hom.:

12140

Bravo

AF:

0.178

TwinsUK

AF:

0.295

AC:

1093

ALSPAC

AF:

0.288

AC:

1109

ESP6500AA

AF:

0.0531

AC:

234

ESP6500EA

AF:

0.268

AC:

2302

ExAC

AF:

0.203

AC:

24590

Asia WGS

AF:

0.120

AC:

418

AN:

3478

EpiCase

AF:

0.266

EpiControl

AF:

0.261

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Combined immunodeficiency due to LRBA deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

.;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.031

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.37

N;N;.

REVEL

Benign

0.044

Sift

Benign

0.33

T;T;.

Sift4G

Benign

0.27

T;T;.

Polyphen

0.049

B;B;.

Vest4

0.46

MPC

0.46

ClinPred

0.015

GERP RS

4.4

Varity_R

0.067

gMVP

0.15

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