chr4-150761851-TA-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1
The NM_001364905.1(LRBA):c.5581-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,221,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)
Exomes 𝑓: 0.018 ( 0 hom. )
Consequence
LRBA
NM_001364905.1 splice_region, splice_polypyrimidine_tract, intron
NM_001364905.1 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.30
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 4-150761851-TA-T is Benign according to our data. Variant chr4-150761851-TA-T is described in ClinVar as [Benign]. Clinvar id is 1165253.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-150761851-TA-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0179 (19309/1076028) while in subpopulation SAS AF= 0.0264 (1383/52454). AF 95% confidence interval is 0.0252. There are 0 homozygotes in gnomad4_exome. There are 9491 alleles in male gnomad4_exome subpopulation. Median coverage is 20. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.5581-5del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.5581-5del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000359 AC: 52AN: 144988Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
52
AN:
144988
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0179 AC: 19309AN: 1076028Hom.: 0 Cov.: 20 AF XY: 0.0179 AC XY: 9491AN XY: 531480
GnomAD4 exome
AF:
AC:
19309
AN:
1076028
Hom.:
Cov.:
20
AF XY:
AC XY:
9491
AN XY:
531480
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000358 AC: 52AN: 145064Hom.: 0 Cov.: 32 AF XY: 0.000326 AC XY: 23AN XY: 70454
GnomAD4 genome
AF:
AC:
52
AN:
145064
Hom.:
Cov.:
32
AF XY:
AC XY:
23
AN XY:
70454
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at