dbSNP rs62344598: LRBA:p.Leu382Leu (chr4-150914212-A-G) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001364905.1(LRBA):c.1144T>C(p.Leu382Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,607,730 control chromosomes in the GnomAD database, including 2,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 810 hom., cov: 31)

Exomes 𝑓: 0.034 ( 1467 hom. )

Consequence

LRBA
NM_001364905.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.93

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 4-150914212-A-G is Benign according to our data. Variant chr4-150914212-A-G is described in ClinVar as [Benign]. Clinvar id is 473165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150914212-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1 link	c.1144T>C	p.Leu382Leu	synonymous_variant	Exon 9 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.1144T>C	p.Leu382Leu	synonymous_variant	Exon 9 of 57		NM_001364905.1	ENSP00000498582.2		A0A494C1L5

Frequencies

GnomAD3 genomes

AF:

0.0751

AC:

11412

AN:

151928

Hom.:

803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0403

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0594

GnomAD3 exomes

AF:

0.0393

AC:

9808

AN:

249438

Hom.:

437

AF XY:

0.0361

AC XY:

4875

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0409

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0384

Gnomad NFE exome

AF:

0.0353

Gnomad OTH exome

AF:

0.0380

GnomAD4 exome

AF:

0.0341

AC:

49652

AN:

1455684

Hom.:

1467

Cov.:

AF XY:

0.0332

AC XY:

24036

AN XY:

724150

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0423

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0391

Gnomad4 NFE exome

AF:

0.0315

Gnomad4 OTH exome

AF:

0.0413

GnomAD4 genome

AF:

0.0753

AC:

11446

AN:

152046

Hom.:

810

Cov.:

AF XY:

0.0732

AC XY:

5441

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.0355

Gnomad4 ASJ

AF:

0.0403

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.0369

Gnomad4 NFE

AF:

0.0324

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0469

Hom.:

201

Bravo

AF:

0.0827

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.4

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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