rs1163872504

chr4-150929074-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_001364905.1(LRBA):c.217-9C>T 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 0.000429 in 1,101,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRBA NM_001364905.1 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001682
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0950

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 Benign. Variant got -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-150929074-G-A is Benign according to our data. Variant chr4-150929074-G-A is described in ClinVar as [Benign]. Clinvar id is 473171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-150929074-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000429 (472/1101270) while in subpopulation AMR AF= 0.00214 (64/29970). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4_exome. There are 239 alleles in male gnomad4_exome subpopulation. Median coverage is 22. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRBA	NM_001364905.1	c.217-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000651943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRBA	ENST00000651943.2	c.217-9C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001364905.1	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 41 AN: 133356 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000227

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00353

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000115

Gnomad OTH AF: 0.000541

GnomAD4 exome AF: 0.000429 AC: 472 AN: 1101270 Hom.: 0 Cov.: 22 AF XY: 0.000435 AC XY: 239 AN XY: 548844

Gnomad4 AFR exome AF: 0.00168

Gnomad4 AMR exome AF: 0.00214

Gnomad4 ASJ exome AF: 0.000708

Gnomad4 EAS exome AF: 0.000200

Gnomad4 SAS exome AF: 0.000734

Gnomad4 FIN exome AF: 0.000396

Gnomad4 NFE exome AF: 0.000310

Gnomad4 OTH exome AF: 0.000395

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000307 AC: 41 AN: 133356 Hom.: 0 Cov.: 31 AF XY: 0.000343 AC XY: 22 AN XY: 64098

Gnomad4 AFR AF: 0.000108

Gnomad4 AMR AF: 0.000227

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00353

Gnomad4 NFE AF: 0.000115

Gnomad4 OTH AF: 0.000541

Alfa AF: 0.00334 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined immunodeficiency due to LRBA deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 11, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.2
Dann	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs1163872504; hg19: chr4-151850226;