4-150265859-A-AGAGAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001364905.1(LRBA):c.8469-48_8469-47insATCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,213,366 control chromosomes in the GnomAD database, including 1,164 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (198 hom., cov: 32)
  • Exomes 𝑓: 0.026 (966 hom.)
• Consequence: LRBA NM_001364905.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.624

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-150265859-A-AGAGAT is Benign according to our data. Variant chr4-150265859-A-AGAGAT is described in ClinVar as [Benign]. Clinvar id is 1265200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRBA	NM_001364905.1	c.8469-48_8469-47insATCTC		intron_variant		ENST00000651943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRBA	ENST00000651943.2	c.8469-48_8469-47insATCTC		intron_variant			NM_001364905.1	P3

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5483 AN: 152154 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0404 AC: 9720 AN: 240762 Hom.: 393 AF XY: 0.0377 AC XY: 4897 AN XY: 130050

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.0877

Gnomad ASJ exome AF: 0.0386

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.0385

Gnomad FIN exome AF: 0.00629

Gnomad NFE exome AF: 0.0165

Gnomad OTH exome AF: 0.0332

GnomAD4 exome AF: 0.0257 AC: 27280 AN: 1061094 Hom.: 966 Cov.: 14 AF XY: 0.0259 AC XY: 14148 AN XY: 545676

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.0337

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.0392

Gnomad4 FIN exome AF: 0.00617

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0272

GnomAD4 genome AF: 0.0360 AC: 5488 AN: 152272 Hom.: 198 Cov.: 32 AF XY: 0.0380 AC XY: 2832 AN XY: 74460

Gnomad4 AFR AF: 0.0415

Gnomad4 AMR AF: 0.0895

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0266 Hom.: 13

Bravo AF: 0.0406

Asia WGS AF: 0.0850 AC: 293 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs150278643; hg19: chr4-151187011;