rs3749574

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.8077G>A(p.Ala2693Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,595,388 control chromosomes in the GnomAD database, including 64,008 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 0.21 ( 4127 hom., cov: 32)

Exomes 𝑓: 0.28 ( 59881 hom. )

Consequence

LRBA
NM_001364905.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.95

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=0.006324917).

BP6

Variant 4-150285975-C-T is Benign according to our data. Variant chr4-150285975-C-T is described in ClinVar as [Benign]. Clinvar id is 403048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1 link	c.8077G>A	p.Ala2693Thr	missense_variant	Exon 54 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.8077G>A	p.Ala2693Thr	missense_variant	Exon 54 of 57		NM_001364905.1	ENSP00000498582.2		A0A494C1L5

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31997

AN:

152008

Hom.:

4127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0718

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.219

GnomAD3 exomes

AF:

0.209

AC:

47361

AN:

226736

Hom.:

5601

AF XY:

0.210

AC XY:

25570

AN XY:

121826

show subpopulations

Gnomad AFR exome

AF:

0.0631

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.279

AC:

402889

AN:

1443262

Hom.:

59881

Cov.:

AF XY:

0.274

AC XY:

196493

AN XY:

716378

show subpopulations

Gnomad4 AFR exome

AF:

0.0642

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.276

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.210

AC:

31992

AN:

152126

Hom.:

4127

Cov.:

AF XY:

0.204

AC XY:

15143

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0716

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.273

Hom.:

12797

Bravo

AF:

0.205

TwinsUK

AF:

0.317

AC:

1176

ALSPAC

AF:

0.313

AC:

1205

ESP6500AA

AF:

0.0792

AC:

349

ESP6500EA

AF:

0.297

AC:

2554

ExAC

AF:

0.205

AC:

24854

Asia WGS

AF:

0.135

AC:

472

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

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 -

Combined immunodeficiency due to LRBA deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 26, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.022

.;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.044

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

.;L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.40

N;N;.

REVEL

Benign

0.087

Sift

Benign

0.24

T;T;.

Sift4G

Benign

0.78

T;T;.

Polyphen

0.0010

B;B;.

Vest4

0.083

MPC

0.11

ClinPred

0.0047

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.059

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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