NM_001364905.1:c.8517C>T

Variant names:

• chr4-150265764-G-A
• rs145690847
• NM_001364905.1:c.8517C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6_Very_Strong BP7

The NM_001364905.1(LRBA):​c.8517C>T​(p.Asn2839Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: LRBA NM_001364905.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.250
• Publications: 0 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: Genomics England PanelApp, Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 4-150265764-G-A is Benign according to our data. Variant chr4-150265764-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 724342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.25 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	NM_001364905.1	MANE Select	c.8517C>T	p.Asn2839Asn	synonymous	Exon 57 of 57	NP_001351834.1	A0A494C1L5
	LRBA	NM_001440430.1		c.8565C>T	p.Asn2855Asn	synonymous	Exon 58 of 58	NP_001427359.1
	LRBA	NM_006726.5		c.8550C>T	p.Asn2850Asn	synonymous	Exon 58 of 58	NP_006717.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	ENST00000651943.2	MANE Select	c.8517C>T	p.Asn2839Asn	synonymous	Exon 57 of 57	ENSP00000498582.2	A0A494C1L5
	LRBA	ENST00000357115.9	TSL:1	c.8550C>T	p.Asn2850Asn	synonymous	Exon 58 of 58	ENSP00000349629.3	P50851-1
	LRBA	ENST00000510413.5	TSL:1	c.8514C>T	p.Asn2838Asn	synonymous	Exon 57 of 57	ENSP00000421552.1	P50851-2

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152092 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000882

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000164 AC: 41 AN: 249244 AF XY: 0.000148

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000627

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000650 AC: 95 AN: 1461388 Hom.: 0 Cov.: 29 AF XY: 0.0000674 AC XY: 49 AN XY: 727050

African (AFR) AF: 0.000777 AC: 26 AN: 33468

American (AMR) AF: 0.000224 AC: 10 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39680

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86232

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111604

Other (OTH) AF: 0.0000994 AC: 6 AN: 60384

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.000417 AC XY: 31 AN XY: 74412

African (AFR) AF: 0.00116 AC: 48 AN: 41522

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68022

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000236 Hom.: 0

Bravo AF: 0.000298

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Combined immunodeficiency due to LRBA deficiency (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.2
DANN	Benign	0.95
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.71	D
PhyloP100		0.25
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs145690847; hg19: chr4-151186916;