4-150371934-T-C

Variant names:

• chr4-150371934-T-C
• rs10520063
• NM_001364905.1:c.7195-21775A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364905.1(LRBA):​c.7195-21775A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,118 control chromosomes in the GnomAD database, including 51,132 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (51132 hom., cov: 31)
• Consequence: LRBA NM_001364905.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 3 publications found

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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1	c.7195-21775A>G		intron_variant	Intron 47 of 56	ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2	c.7195-21775A>G		intron_variant	Intron 47 of 56		NM_001364905.1	ENSP00000498582.2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123212 AN: 152000 Hom.: 51123 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.818

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.810 AC: 123255 AN: 152118 Hom.: 51132 Cov.: 31 AF XY: 0.801 AC XY: 59561 AN XY: 74374

African (AFR) AF: 0.668 AC: 27729 AN: 41480

American (AMR) AF: 0.751 AC: 11467 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2889 AN: 3472

East Asian (EAS) AF: 0.706 AC: 3649 AN: 5166

South Asian (SAS) AF: 0.568 AC: 2736 AN: 4818

European-Finnish (FIN) AF: 0.866 AC: 9145 AN: 10566

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62846 AN: 68018

Other (OTH) AF: 0.814 AC: 1723 AN: 2116

Alfa AF: 0.840 Hom.: 4017

Bravo AF: 0.797

Asia WGS AF: 0.617 AC: 2147 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10520063; hg19: chr4-151293086;