4-150914350-GAA-GA

Position:

• chr4-150914350-GAA-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001364905.1(LRBA):​c.1015-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 858,622 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (26 hom., cov: 32)
  • Exomes 𝑓: 0.051 (20 hom.)
• Consequence: LRBA NM_001364905.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.262

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 4-150914350-GA-G is Benign according to our data. Variant chr4-150914350-GA-G is described in ClinVar as [Benign]. Clinvar id is 522233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150914350-GA-G is described in Lovd as [Benign]. Variant chr4-150914350-GA-G is described in Lovd as [Benign]. Variant chr4-150914350-GA-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRBA	NM_001364905.1	c.1015-10delT		intron_variant		ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2	c.1015-10delT		intron_variant			NM_001364905.1	ENSP00000498582.2

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 1591 AN: 99488 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00490

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000558

Gnomad SAS AF: 0.000932

Gnomad FIN AF: 0.00326

Gnomad MID AF: 0.00472

Gnomad NFE AF: 0.000835

Gnomad OTH AF: 0.0131

GnomAD4 exome AF: 0.0514 AC: 38999 AN: 759126 Hom.: 20 Cov.: 20 AF XY: 0.0536 AC XY: 19681 AN XY: 367254

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0987

Gnomad4 ASJ exome AF: 0.0763

Gnomad4 EAS exome AF: 0.0737

Gnomad4 SAS exome AF: 0.0941

Gnomad4 FIN exome AF: 0.0614

Gnomad4 NFE exome AF: 0.0449

Gnomad4 OTH exome AF: 0.0610

GnomAD4 genome AF: 0.0160 AC: 1592 AN: 99496 Hom.: 26 Cov.: 32 AF XY: 0.0152 AC XY: 736 AN XY: 48464

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.00480

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000560

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00326

Gnomad4 NFE AF: 0.000858

Gnomad4 OTH AF: 0.0130

Alfa AF: 0.000127 Hom.: 0

Bravo AF: 0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined immunodeficiency due to LRBA deficiency Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jul 19, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs753223643; hg19: chr4-151835502;