Variant 4-150761851-TAAA-TAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_001364905.1(LRBA):c.5581-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,221,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.018 ( 0 hom. )

Consequence

LRBA
NM_001364905.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 4-150761851-TA-T is Benign according to our data. Variant chr4-150761851-TA-T is described in ClinVar as [Benign]. Clinvar id is 1165253.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-150761851-TA-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0179 (19309/1076028) while in subpopulation SAS AF= 0.0264 (1383/52454). AF 95% confidence interval is 0.0252. There are 0 homozygotes in gnomad4_exome. There are 9491 alleles in male gnomad4_exome subpopulation. Median coverage is 20. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRBA	NM_001364905.1 linkuse as main transcript	c.5581-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000651943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRBA	ENST00000651943.2 linkuse as main transcript	c.5581-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001364905.1	P3

Frequencies

GnomAD3 genomes

AF:

0.000359

AC:

AN:

144988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.000219

Gnomad FIN

AF:

0.00269

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.000168

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0179

AC:

19309

AN:

1076028

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

9491

AN XY:

531480

show subpopulations

Gnomad4 AFR exome

AF:

0.0190

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.0264

Gnomad4 FIN exome

AF:

0.00865

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.000358

AC:

AN:

145064

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

AN XY:

70454

show subpopulations

Gnomad4 AFR

AF:

0.000201

Gnomad4 AMR

AF:

0.000347

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.000220

Gnomad4 FIN

AF:

0.00269

Gnomad4 NFE

AF:

0.000168

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Combined immunodeficiency due to LRBA deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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