rs753223643

Positions:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001364905.1(LRBA):​c.1015-11_1015-10del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000237 (217/916290) while in subpopulation SAS AF= 0.000858 (31/36112). AF 95% confidence interval is 0.000621. There are 0 homozygotes in gnomad4_exome. There are 113 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRBA	NM_001364905.1	c.1015-11_1015-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000651943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRBA	ENST00000651943.2	c.1015-11_1015-10del		splice_polypyrimidine_tract_variant, intron_variant			NM_001364905.1	P3

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

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

Gnomad4 AFR exome AF: 0.000245

Gnomad4 AMR exome AF: 0.000513

Gnomad4 ASJ exome AF: 0.000432

Gnomad4 EAS exome AF: 0.000445

Gnomad4 SAS exome AF: 0.000858

Gnomad4 FIN exome AF: 0.000279

Gnomad4 NFE exome AF: 0.000189

Gnomad4 OTH exome AF: 0.000221

GnomAD4 genome AF: 0.0000100 AC: 1 AN: 99634 Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 1 AN XY: 48514

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000225

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs753223643; hg19: chr4-151835502;