rs769037604

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001364905.1(LRBA):c.545G>A(p.Arg182Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,610,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LRBA
NM_001364905.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Publications

2 publications found

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]

LRBA Gene-Disease associations (from GenCC):

combined immunodeficiency due to LRBA deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

LRBA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07503006).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364905.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRBA	NM_001364905.1	MANE Select	c.545G>A	p.Arg182Gln	missense	Exon 4 of 57	NP_001351834.1	A0A494C1L5
LRBA	NM_001440430.1		c.545G>A	p.Arg182Gln	missense	Exon 4 of 58	NP_001427359.1
LRBA	NM_006726.5		c.545G>A	p.Arg182Gln	missense	Exon 4 of 58	NP_006717.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRBA	ENST00000651943.2	MANE Select	c.545G>A	p.Arg182Gln	missense	Exon 4 of 57	ENSP00000498582.2	A0A494C1L5
LRBA	ENST00000357115.9	TSL:1	c.545G>A	p.Arg182Gln	missense	Exon 4 of 58	ENSP00000349629.3	P50851-1
LRBA	ENST00000510413.5	TSL:1	c.545G>A	p.Arg182Gln	missense	Exon 4 of 57	ENSP00000421552.1	P50851-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

249312

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1458036

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33316

American (AMR)

AF:

0.00

AC:

AN:

44198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

85832

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1109628

Other (OTH)

AF:

0.00

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined immunodeficiency due to LRBA deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.46

M_CAP

Benign

0.018

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PhyloP100

2.3

PrimateAI

Benign

0.41

PROVEAN

Benign

0.73

REVEL

Benign

0.029

Sift

Benign

0.45

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.21

MutPred

0.40

Loss of MoRF binding (P = 0.0325)

MVP

0.25

MPC

0.13

ClinPred

0.14

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over