4-150831981-GAA-GA

Variant names:

• chr4-150831981-GA-G
• rs145452262
• NM_001364905.1:c.4570-6delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001364905.1(LRBA):​c.4570-6delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,462,342 control chromosomes in the GnomAD database, including 1,520 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (832 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (688 hom.)
• Consequence: LRBA NM_001364905.1 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.178
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to LRBA deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-150831981-GA-G is Benign according to our data. Variant chr4-150831981-GA-G is described in ClinVar as Benign. ClinVar VariationId is 473178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364905.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	NM_001364905.1	MANE Select	c.4570-6delT		splice_region intron	N/A	NP_001351834.1
	LRBA	NM_001440430.1		c.4570-6delT		splice_region intron	N/A	NP_001427359.1
	LRBA	NM_006726.5		c.4570-6delT		splice_region intron	N/A	NP_006717.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	ENST00000651943.2	MANE Select	c.4570-6delT		splice_region intron	N/A	ENSP00000498582.2
	LRBA	ENST00000357115.9	TSL:1	c.4570-6delT		splice_region intron	N/A	ENSP00000349629.3
	LRBA	ENST00000510413.5	TSL:1	c.4570-6delT		splice_region intron	N/A	ENSP00000421552.1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9091 AN: 151238 Hom.: 825 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0318

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.0525

GnomAD2 exomes AF: 0.0178 AC: 3376 AN: 189546 AF XY: 0.0132

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.000155

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00124

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.00652 AC: 8544 AN: 1310986 Hom.: 688 Cov.: 27 AF XY: 0.00588 AC XY: 3770 AN XY: 641702

African (AFR) AF: 0.205 AC: 5840 AN: 28426

American (AMR) AF: 0.0139 AC: 378 AN: 27234

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 702 AN: 22048

East Asian (EAS) AF: 0.0000851 AC: 3 AN: 35264

South Asian (SAS) AF: 0.000533 AC: 32 AN: 60022

European-Finnish (FIN) AF: 0.0000804 AC: 4 AN: 49748

Middle Eastern (MID) AF: 0.00977 AC: 51 AN: 5220

European-Non Finnish (NFE) AF: 0.000647 AC: 666 AN: 1029656

Other (OTH) AF: 0.0163 AC: 868 AN: 53368

GnomAD4 genome AF: 0.0603 AC: 9123 AN: 151356 Hom.: 832 Cov.: 31 AF XY: 0.0584 AC XY: 4315 AN XY: 73914

African (AFR) AF: 0.204 AC: 8409 AN: 41278

American (AMR) AF: 0.0272 AC: 414 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 110 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000627 AC: 3 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10346

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.00111 AC: 75 AN: 67826

Other (OTH) AF: 0.0519 AC: 109 AN: 2100

Alfa AF: 0.00811 Hom.: 14

Bravo AF: 0.0684

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs145452262; hg19: chr4-151753133; COSMIC: COSV100841483;