4-150905904-G-T

Variant summary

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

The NM_001364905.1(LRBA):​c.1689C>A​(p.Pro563=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000729 in 1,613,562 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 7 hom., cov: 31)
Exomes 𝑓: 0.00038 ( 3 hom. )

Consequence

LRBA
NM_001364905.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 4-150905904-G-T is Benign according to our data. Variant chr4-150905904-G-T is described in ClinVar as [Benign]. Clinvar id is 540404.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-150905904-G-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.17 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00412 (627/152240) while in subpopulation AFR AF= 0.0144 (600/41538). AF 95% confidence interval is 0.0135. There are 7 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRBANM_001364905.1 linkuse as main transcriptc.1689C>A p.Pro563= synonymous_variant 13/57 ENST00000651943.2 NP_001351834.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRBAENST00000651943.2 linkuse as main transcriptc.1689C>A p.Pro563= synonymous_variant 13/57 NM_001364905.1 ENSP00000498582 P3

Frequencies

GnomAD3 genomes
AF:
0.00415
AC:
631
AN:
152122
Hom.:
7
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0146
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
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:
0.0000147
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00104
AC:
261
AN:
250950
Hom.:
2
AF XY:
0.000708
AC XY:
96
AN XY:
135616
show subpopulations
Gnomad AFR exome
AF:
0.0145
Gnomad AMR exome
AF:
0.000724
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000376
AC:
550
AN:
1461322
Hom.:
3
Cov.:
30
AF XY:
0.000316
AC XY:
230
AN XY:
726972
show subpopulations
Gnomad4 AFR exome
AF:
0.0135
Gnomad4 AMR exome
AF:
0.000939
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.000778
GnomAD4 genome
AF:
0.00412
AC:
627
AN:
152240
Hom.:
7
Cov.:
31
AF XY:
0.00383
AC XY:
285
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0144
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00146
Hom.:
1
Bravo
AF:
0.00482
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Combined immunodeficiency due to LRBA deficiency Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -
LRBA-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJun 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
6.3
DANN
Benign
0.66

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: rs115894255; hg19: chr4-151827056; API