4-150588054-GTC-ATG

Variant names:

• chr4-150588054-GTC-ATG
• NM_001364905.1:c.6322_6324delGACinsCAT
• LRBA p.Asp2108His

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001364905.1(LRBA):​c.6322_6324delGACinsCAT​(p.Asp2108His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2108N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRBA NM_001364905.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.01
• Publications: 0 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	NM_001364905.1	MANE Select	c.6322_6324delGACinsCAT	p.Asp2108His	missense	N/A	NP_001351834.1	A0A494C1L5
	LRBA	NM_001440430.1		c.6355_6357delGACinsCAT	p.Asp2119His	missense	N/A	NP_001427359.1
	LRBA	NM_006726.5		c.6355_6357delGACinsCAT	p.Asp2119His	missense	N/A	NP_006717.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	ENST00000651943.2	MANE Select	c.6322_6324delGACinsCAT	p.Asp2108His	missense	N/A	ENSP00000498582.2	A0A494C1L5
	LRBA	ENST00000357115.9	TSL:1	c.6355_6357delGACinsCAT	p.Asp2119His	missense	N/A	ENSP00000349629.3	P50851-1
	LRBA	ENST00000510413.5	TSL:1	c.6322_6324delGACinsCAT	p.Asp2108His	missense	N/A	ENSP00000421552.1	P50851-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-151509206;