4-150831981-GAA-GAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001364905.1(LRBA):​c.4570-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,462,620 control chromosomes in the GnomAD database, including 4 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (4 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-G-GA is Benign according to our data. Variant chr4-150831981-G-GA is described in ClinVar as Benign. ClinVar VariationId is 1168176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000119 (18/151378) while in subpopulation SAS AF = 0.00292 (14/4788). AF 95% confidence interval is 0.00177. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.4570-6dupT		splice_region intron	N/A	NP_001351834.1
	LRBA	NM_001440430.1		c.4570-6dupT		splice_region intron	N/A	NP_001427359.1
	LRBA	NM_006726.5		c.4570-6dupT		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.4570-6dupT		splice_region intron	N/A	ENSP00000498582.2
	LRBA	ENST00000357115.9	TSL:1	c.4570-6dupT		splice_region intron	N/A	ENSP00000349629.3
	LRBA	ENST00000510413.5	TSL:1	c.4570-6dupT		splice_region intron	N/A	ENSP00000421552.1

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151260 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00292

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000301 AC: 57 AN: 189546 AF XY: 0.000374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000318

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000170 AC: 223 AN: 1311242 Hom.: 4 Cov.: 27 AF XY: 0.000204 AC XY: 131 AN XY: 641824

African (AFR) AF: 0.00 AC: 0 AN: 28468

American (AMR) AF: 0.0000367 AC: 1 AN: 27250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22062

East Asian (EAS) AF: 0.00 AC: 0 AN: 35276

South Asian (SAS) AF: 0.00243 AC: 146 AN: 60062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49754

Middle Eastern (MID) AF: 0.000575 AC: 3 AN: 5220

European-Non Finnish (NFE) AF: 0.0000612 AC: 63 AN: 1029764

Other (OTH) AF: 0.000187 AC: 10 AN: 53386

GnomAD4 genome AF: 0.000119 AC: 18 AN: 151378 Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10 AN XY: 73928

African (AFR) AF: 0.00 AC: 0 AN: 41300

American (AMR) AF: 0.00 AC: 0 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

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

South Asian (SAS) AF: 0.00292 AC: 14 AN: 4788

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67826

Other (OTH) AF: 0.000476 AC: 1 AN: 2100

Alfa AF: 0.00 Hom.: 14

Bravo AF: 0.0000302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined immunodeficiency due to LRBA deficiency Benign:1

Oct 16, 2024

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		=98/2	polymorphism

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;