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GeneBe

rs78563281

chr4-150285964-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001364905.1(LRBA):c.8088G>A(p.Ala2696=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,596,852 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00049 ( 6 hom. )

Consequence

LRBA
NM_001364905.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.34
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-150285964-C-T is Benign according to our data. Variant chr4-150285964-C-T is described in ClinVar as [Benign]. Clinvar id is 473188.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-150285964-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.34 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00512 (779/152248) while in subpopulation AFR AF= 0.0179 (745/41514). AF 95% confidence interval is 0.0169. There are 8 homozygotes in gnomad4. There are 356 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRBANM_001364905.1 linkuse as main transcriptc.8088G>A p.Ala2696= synonymous_variant 54/57 ENST00000651943.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRBAENST00000651943.2 linkuse as main transcriptc.8088G>A p.Ala2696= synonymous_variant 54/57 NM_001364905.1 P3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00513
AC:
781
AN:
152130
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
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:
0.0000588
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00120
AC:
272
AN:
226810
Hom.:
3
AF XY:
0.000836
AC XY:
102
AN XY:
121982
show subpopulations
Gnomad AFR exome
AF:
0.0162
Gnomad AMR exome
AF:
0.000973
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000371
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000488
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000490
AC:
708
AN:
1444604
Hom.:
6
Cov.:
29
AF XY:
0.000420
AC XY:
301
AN XY:
717210
show subpopulations
Gnomad4 AFR exome
AF:
0.0168
Gnomad4 AMR exome
AF:
0.00111
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000163
Gnomad4 OTH exome
AF:
0.00137
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00512
AC:
779
AN:
152248
Hom.:
8
Cov.:
33
AF XY:
0.00478
AC XY:
356
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0179
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00230
Hom.:
4
Bravo
AF:
0.00596
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

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 submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
0.29
Dann
Benign
0.64
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs78563281; hg19: chr4-151207116; API