rs753223643

Variant names:

• chr4-150914350-GAAA-G
• rs753223643
• NM_001364905.1:c.1015-12_1015-10delTTT

Your query was ambiguous. Multiple possible variants found:

• chr4-150914350-GAAA-G
• chr4-150914350-GAAA-GA
• chr4-150914350-GAAA-GAA
• chr4-150914350-GAAA-GAAAA
• chr4-150914350-GAAA-GAAAAA
• chr4-150914350-GAAA-GAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001364905.1(LRBA):​c.1015-12_1015-10delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000976 in 921,816 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: LRBA NM_001364905.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1	c.1015-12_1015-10delTTT		intron_variant	Intron 8 of 56	ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2	c.1015-12_1015-10delTTT		intron_variant	Intron 8 of 56		NM_001364905.1	ENSP00000498582.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000976 AC: 9 AN: 921816 Hom.: 0 AF XY: 0.0000111 AC XY: 5 AN XY: 448974

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000487 AC: 1 AN: 20552

American (AMR) AF: 0.00 AC: 0 AN: 17696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13964

East Asian (EAS) AF: 0.0000402 AC: 1 AN: 24904

South Asian (SAS) AF: 0.0000274 AC: 1 AN: 36454

European-Finnish (FIN) AF: 0.0000308 AC: 1 AN: 32460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3682

European-Non Finnish (NFE) AF: 0.00000544 AC: 4 AN: 735606

Other (OTH) AF: 0.0000274 AC: 1 AN: 36498

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	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: rs753223643; hg19: chr4-151835502;