Variant rs143754610 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001364905.1(LRBA):c.1603-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,608,056 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 136 hom., cov: 31)

Exomes 𝑓: 0.0093 ( 558 hom. )

Consequence

LRBA
NM_001364905.1 splice_region, intron

Scores

Splicing: ADA: 0.00001193

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.430

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-150905994-C-A is Benign according to our data. Variant chr4-150905994-C-A is described in ClinVar as [Benign]. Clinvar id is 473168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150905994-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRBA	NM_001364905.1 linkuse as main transcript	c.1603-4G>T		splice_region_variant, intron_variant		ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2 linkuse as main transcript	c.1603-4G>T		splice_region_variant, intron_variant			NM_001364905.1	ENSP00000498582.2		A0A494C1L5

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2626

AN:

151734

Hom.:

135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0560

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0482

Gnomad SAS

AF:

0.00354

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00311

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0281

AC:

6925

AN:

246602

Hom.:

307

AF XY:

0.0244

AC XY:

3249

AN XY:

133382

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.0890

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0533

Gnomad SAS exome

AF:

0.000772

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.00925

AC:

13473

AN:

1456204

Hom.:

558

Cov.:

AF XY:

0.00873

AC XY:

6322

AN XY:

724400

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.0883

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.0496

Gnomad4 SAS exome

AF:

0.000985

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.00970

GnomAD4 genome

AF:

0.0173

AC:

2627

AN:

151852

Hom.:

136

Cov.:

AF XY:

0.0232

AC XY:

1723

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.00162

Gnomad4 AMR

AF:

0.0561

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0477

Gnomad4 SAS

AF:

0.00354

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.00311

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00490

Hom.:

Bravo

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined immunodeficiency due to LRBA deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.7

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

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