rs186080

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:9O:1

Conservation

PhyloP100: -0.464

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

combined immunodeficiency due to LRBA deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

LRBA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 196133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1 link	c.4569+9C>T		intron_variant	Intron 28 of 56	ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2 link	c.4569+9C>T		intron_variant	Intron 28 of 56		NM_001364905.1	ENSP00000498582.2

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

GnomAD2 exomes

AF:

0.862

AC:

216072

AN:

250696

AF XY:

0.863

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 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

African (AFR)

AF:

0.618

AC:

19728

AN:

31900

American (AMR)

AF:

0.848

AC:

37709

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

22435

AN:

25440

East Asian (EAS)

AF:

0.878

AC:

34431

AN:

39212

South Asian (SAS)

AF:

0.737

AC:

61068

AN:

82826

European-Finnish (FIN)

AF:

0.852

AC:

44994

AN:

52834

Middle Eastern (MID)

AF:

0.894

AC:

4992

AN:

5584

European-Non Finnish (NFE)

AF:

0.945

AC:

986145

AN:

1043810

Other (OTH)

AF:

0.891

AC:

51341

AN:

57630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4819

9639

14458

19278

24097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19850

39700

59550

79400

99250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.831

AC:

126375

AN:

151994

Hom.:

53770

Cov.:

AF XY:

0.826

AC XY:

61358

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.634

AC:

26258

AN:

41396

American (AMR)

AF:

0.860

AC:

13139

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.888

AC:

3079

AN:

3468

East Asian (EAS)

AF:

0.875

AC:

4534

AN:

5182

South Asian (SAS)

AF:

0.727

AC:

3488

AN:

4798

European-Finnish (FIN)

AF:

0.846

AC:

8929

AN:

10558

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.941

AC:

64014

AN:

68002

Other (OTH)

AF:

0.854

AC:

1806

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

967

1934

2901

3868

4835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.900

Hom.:

190361

Bravo

AF:

0.825

Asia WGS

AF:

0.760

AC:

2639

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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 -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 10, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

May 26, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Aug 19, 2021

Genome-Nilou Lab

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

- -

not provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.0

(source)

DANN

Benign

0.65

PhyloP100

-0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over