rs35612775

Positions:

chr4-150906386-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001364905.1(LRBA):c.1513A>G(p.Ile505Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,606,962 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00055 ( 8 hom. )

Consequence

LRBA
NM_001364905.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.325

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059100688).

BP6

Variant 4-150906386-T-C is Benign according to our data. Variant chr4-150906386-T-C is described in ClinVar as [Benign]. Clinvar id is 540402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-150906386-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00587 (894/152316) while in subpopulation AFR AF= 0.0199 (829/41580). AF 95% confidence interval is 0.0188. There are 6 homozygotes in gnomad4. There are 427 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRBA	NM_001364905.1 linkuse as main transcript	c.1513A>G	p.Ile505Val	missense_variant	12/57	ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2 linkuse as main transcript	c.1513A>G	p.Ile505Val	missense_variant	12/57		NM_001364905.1	ENSP00000498582	P3

Frequencies

GnomAD3 genomes

AF:

0.00584

AC:

889

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

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:

0.0000441

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00146

AC:

365

AN:

249880

Hom.:

AF XY:

0.00113

AC XY:

152

AN XY:

134950

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.000817

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:

0.0000177

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000553

AC:

805

AN:

1454646

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

327

AN XY:

723882

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000585

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00587

AC:

894

AN:

152316

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

427

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00269

Hom.:

Bravo

AF:

0.00705

ESP6500AA

AF:

0.0195

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00193

AC:

234

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined immunodeficiency due to LRBA deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 21, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.034

.;T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.29

N;N;.

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.69

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.26

MVP

0.38

MPC

0.095

ClinPred

0.0022

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over