Variant 4-150914350-GAA-GAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001364905.1(LRBA):c.1015-10_1015-9insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 921,400 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.035 ( 7 hom. )

Consequence

LRBA
NM_001364905.1 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.262

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 -10 ACMG points.

BP6

Variant 4-150914350-G-GA is Benign according to our data. Variant chr4-150914350-G-GA is described in ClinVar as [Benign]. Clinvar id is 473164.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00497 (495/99596) while in subpopulation AMR AF= 0.00666 (68/10214). AF 95% confidence interval is 0.00539. There are 0 homozygotes in gnomad4. There are 244 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRBA	NM_001364905.1 linkuse as main transcript	c.1015-10_1015-9insT		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.1015-10_1015-9insT		splice_polypyrimidine_tract_variant, intron_variant			NM_001364905.1	P3

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

495

AN:

99588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00666

Gnomad ASJ

AF:

0.00495

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00218

Gnomad FIN

AF:

0.00617

Gnomad MID

AF:

0.00472

Gnomad NFE

AF:

0.00480

Gnomad OTH

AF:

0.00436

GnomAD4 exome

AF:

0.0351

AC:

28846

AN:

821804

Hom.:

Cov.:

AF XY:

0.0346

AC XY:

13832

AN XY:

400182

show subpopulations

Gnomad4 AFR exome

AF:

0.0352

Gnomad4 AMR exome

AF:

0.0337

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.0244

Gnomad4 SAS exome

AF:

0.0424

Gnomad4 FIN exome

AF:

0.0243

Gnomad4 NFE exome

AF:

0.0359

Gnomad4 OTH exome

AF:

0.0314

GnomAD4 genome

AF:

0.00497

AC:

495

AN:

99596

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

244

AN XY:

48508

show subpopulations

Gnomad4 AFR

AF:

0.00542

Gnomad4 AMR

AF:

0.00666

Gnomad4 ASJ

AF:

0.00495

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00219

Gnomad4 FIN

AF:

0.00617

Gnomad4 NFE

AF:

0.00480

Gnomad4 OTH

AF:

0.00433

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 31, 2024

- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

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