4-150914350-GAAA-GA

Variant names:

• chr4-150914350-GAA-G
• rs753223643
• NM_001364905.1:c.1015-11_1015-10delTT

Variant summary

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

The NM_001364905.1(LRBA):​c.1015-11_1015-10delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,015,924 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: 𝑓 0.000010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: LRBA NM_001364905.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1	c.1015-11_1015-10delTT		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.1015-11_1015-10delTT		intron_variant	Intron 8 of 56		NM_001364905.1	ENSP00000498582.2

Frequencies

GnomAD3 genomes AF: 0.0000100 AC: 1 AN: 99634 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000225

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000895 AC: 55 AN: 61426 AF XY: 0.000830

Gnomad AFR exome AF: 0.000629

Gnomad AMR exome AF: 0.00204

Gnomad ASJ exome AF: 0.00202

Gnomad EAS exome AF: 0.00176

Gnomad FIN exome AF: 0.000144

Gnomad NFE exome AF: 0.000698

Gnomad OTH exome AF: 0.000762

GnomAD4 exome AF: 0.000237 AC: 217 AN: 916290 Hom.: 0 AF XY: 0.000253 AC XY: 113 AN XY: 446218

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

African (AFR) AF: 0.000245 AC: 5 AN: 20416

American (AMR) AF: 0.000513 AC: 9 AN: 17540

Ashkenazi Jewish (ASJ) AF: 0.000432 AC: 6 AN: 13878

East Asian (EAS) AF: 0.000445 AC: 11 AN: 24732

South Asian (SAS) AF: 0.000858 AC: 31 AN: 36112

European-Finnish (FIN) AF: 0.000279 AC: 9 AN: 32280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3660

European-Non Finnish (NFE) AF: 0.000189 AC: 138 AN: 731408

Other (OTH) AF: 0.000221 AC: 8 AN: 36264

⚠️ 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 AF: 0.0000100 AC: 1 AN: 99634 Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 1 AN XY: 48514

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

African (AFR) AF: 0.00 AC: 0 AN: 27632

American (AMR) AF: 0.00 AC: 0 AN: 10206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2220

East Asian (EAS) AF: 0.00 AC: 0 AN: 3588

South Asian (SAS) AF: 0.00 AC: 0 AN: 3218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.0000225 AC: 1 AN: 44394

Other (OTH) AF: 0.00 AC: 0 AN: 1376

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
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;