rs62344598

Variant names:

• chr4-150914212-A-G
• rs62344598
• NM_001364905.1:c.1144T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-150914212-A-G
• chr4-150914212-A-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001364905.1(LRBA):​c.1144T>C​(p.Leu382Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,607,730 control chromosomes in the GnomAD database, including 2,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L382L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.075 (810 hom., cov: 31)
  • Exomes 𝑓: 0.034 (1467 hom.)
• Consequence: LRBA NM_001364905.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.93
• Publications: 6 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 4-150914212-A-G is Benign according to our data. Variant chr4-150914212-A-G is described in ClinVar as Benign. ClinVar VariationId is 473165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRBA	NM_001364905.1	c.1144T>C	p.Leu382Leu	synonymous_variant	Exon 9 of 57	ENST00000651943.2	NP_001351834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRBA	ENST00000651943.2	c.1144T>C	p.Leu382Leu	synonymous_variant	Exon 9 of 57		NM_001364905.1	ENSP00000498582.2

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11412 AN: 151928 Hom.: 803 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0594

GnomAD2 exomes AF: 0.0393 AC: 9808 AN: 249438 AF XY: 0.0361

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.0234

Gnomad ASJ exome AF: 0.0409

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.0384

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0380

GnomAD4 exome AF: 0.0341 AC: 49652 AN: 1455684 Hom.: 1467 Cov.: 31 AF XY: 0.0332 AC XY: 24036 AN XY: 724150

African (AFR) AF: 0.201 AC: 6673 AN: 33214

American (AMR) AF: 0.0258 AC: 1139 AN: 44222

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 1095 AN: 25890

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39626

South Asian (SAS) AF: 0.0107 AC: 911 AN: 85150

European-Finnish (FIN) AF: 0.0391 AC: 2077 AN: 53082

Middle Eastern (MID) AF: 0.0597 AC: 343 AN: 5746

European-Non Finnish (NFE) AF: 0.0315 AC: 34935 AN: 1108682

Other (OTH) AF: 0.0413 AC: 2478 AN: 60072

GnomAD4 genome AF: 0.0753 AC: 11446 AN: 152046 Hom.: 810 Cov.: 31 AF XY: 0.0732 AC XY: 5441 AN XY: 74352

African (AFR) AF: 0.191 AC: 7930 AN: 41416

American (AMR) AF: 0.0355 AC: 542 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4826

European-Finnish (FIN) AF: 0.0369 AC: 391 AN: 10584

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0324 AC: 2205 AN: 67972

Other (OTH) AF: 0.0588 AC: 124 AN: 2108

Alfa AF: 0.0488 Hom.: 260

Bravo AF: 0.0827

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Combined immunodeficiency due to LRBA deficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.4
DANN	Benign	0.76
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs62344598; hg19: chr4-151835364; COSMIC: COSV63950617;