chr4-150310219-T-C

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.7849+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,594,122 control chromosomes in the GnomAD database, including 340,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29855 hom., cov: 32)

Exomes 𝑓: 0.65 ( 310566 hom. )

Consequence

LRBA
NM_001364905.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.645

Publications

14 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=-0.72).

BP6

Variant 4-150310219-T-C is Benign according to our data. Variant chr4-150310219-T-C is described in ClinVar as Benign. ClinVar VariationId is 403049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1 link	c.7849+10A>G		intron_variant	Intron 52 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.7849+10A>G		intron_variant	Intron 52 of 56		NM_001364905.1	ENSP00000498582.2		A0A494C1L5

Frequencies

GnomAD3 genomes

AF:

0.623

AC:

94532

AN:

151844

Hom.:

29850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.576

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.675

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.685

Gnomad OTH

AF:

0.624

GnomAD2 exomes

AF:

0.596

AC:

148419

AN:

248818

AF XY:

0.601

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.423

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.432

Gnomad FIN exome

AF:

0.674

Gnomad NFE exome

AF:

0.687

Gnomad OTH exome

AF:

0.613

GnomAD4 exome

AF:

0.651

AC:

938915

AN:

1442160

Hom.:

310566

Cov.:

AF XY:

0.648

AC XY:

465333

AN XY:

718182

show subpopulations

African (AFR)

AF:

0.580

AC:

19168

AN:

33028

American (AMR)

AF:

0.435

AC:

19295

AN:

44336

Ashkenazi Jewish (ASJ)

AF:

0.680

AC:

17595

AN:

25860

East Asian (EAS)

AF:

0.457

AC:

18066

AN:

39540

South Asian (SAS)

AF:

0.484

AC:

41242

AN:

85150

European-Finnish (FIN)

AF:

0.681

AC:

36063

AN:

52958

Middle Eastern (MID)

AF:

0.630

AC:

3506

AN:

5566

European-Non Finnish (NFE)

AF:

0.681

AC:

746506

AN:

1096050

Other (OTH)

AF:

0.628

AC:

37474

AN:

59672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

14471

28942

43414

57885

72356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18856

37712

56568

75424

94280

<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:

0.622

AC:

94572

AN:

151962

Hom.:

29855

Cov.:

AF XY:

0.617

AC XY:

45811

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.575

AC:

23856

AN:

41468

American (AMR)

AF:

0.536

AC:

8173

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

2316

AN:

3466

East Asian (EAS)

AF:

0.434

AC:

2237

AN:

5160

South Asian (SAS)

AF:

0.472

AC:

2268

AN:

4804

European-Finnish (FIN)

AF:

0.675

AC:

7124

AN:

10550

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.685

AC:

46517

AN:

67956

Other (OTH)

AF:

0.623

AC:

1311

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1805

3609

5414

7218

9023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.658

Hom.:

125975

Bravo

AF:

0.607

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -

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

Significance:Benign

Review Status:no assertion criteria provided

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

- -

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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. -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.65

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