NM_001364905.1:c.5989C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001364905.1(LRBA):c.5989C>T(p.Arg1997Cys) variant causes a missense change. The variant allele was found at a frequency of 0.027 in 1,613,952 control chromosomes in the GnomAD database, including 708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 51 hom., cov: 32)

Exomes 𝑓: 0.028 ( 657 hom. )

Consequence

LRBA
NM_001364905.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.22

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=0.012158245).

BP6

Variant 4-150599064-G-A is Benign according to our data. Variant chr4-150599064-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150599064-G-A is described in Lovd as [Likely_benign]. Variant chr4-150599064-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.021 (3202/152198) while in subpopulation NFE AF= 0.0313 (2127/68010). AF 95% confidence interval is 0.0302. There are 51 homozygotes in gnomad4. There are 1558 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1 link	c.5989C>T	p.Arg1997Cys	missense_variant	Exon 38 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.5989C>T	p.Arg1997Cys	missense_variant	Exon 38 of 57		NM_001364905.1	ENSP00000498582.2		A0A494C1L5

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3201

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00995

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0313

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0239

AC:

6007

AN:

251238

Hom.:

104

AF XY:

0.0247

AC XY:

3350

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.0382

Gnomad NFE exome

AF:

0.0353

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0276

AC:

40351

AN:

1461754

Hom.:

657

Cov.:

AF XY:

0.0273

AC XY:

19829

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00427

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0220

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.0387

Gnomad4 NFE exome

AF:

0.0308

Gnomad4 OTH exome

AF:

0.0269

GnomAD4 genome

AF:

0.0210

AC:

3202

AN:

152198

Hom.:

Cov.:

AF XY:

0.0209

AC XY:

1558

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00542

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.0208

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0360

Gnomad4 NFE

AF:

0.0313

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0283

Hom.:

121

Bravo

AF:

0.0199

TwinsUK

AF:

0.0302

AC:

112

ALSPAC

AF:

0.0285

AC:

110

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0323

AC:

278

ExAC

AF:

0.0253

AC:

3070

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0311

EpiControl

AF:

0.0313

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely 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 -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Combined immunodeficiency due to LRBA deficiency

Benign:2

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

0.16

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

.;T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.4

D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.61

MPC

0.61

ClinPred

0.020

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.47

gMVP

0.78

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