rs145198687

Variant names:

• chr4-150896397-A-G
• rs145198687
• NM_001364905.1:c.2064T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001364905.1(LRBA):​c.2064T>C​(p.His688His) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000376 in 1,487,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: LRBA NM_001364905.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.17
• 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 4-150896397-A-G is Benign according to our data. Variant chr4-150896397-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 540417.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2064T>C	p.His688His	synonymous	Exon 16 of 57	NP_001351834.1	A0A494C1L5
	LRBA	NM_001440430.1		c.2064T>C	p.His688His	synonymous	Exon 16 of 58	NP_001427359.1
	LRBA	NM_006726.5		c.2064T>C	p.His688His	synonymous	Exon 16 of 58	NP_006717.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	ENST00000651943.2	MANE Select	c.2064T>C	p.His688His	synonymous	Exon 16 of 57	ENSP00000498582.2	A0A494C1L5
	LRBA	ENST00000357115.9	TSL:1	c.2064T>C	p.His688His	synonymous	Exon 16 of 58	ENSP00000349629.3	P50851-1
	LRBA	ENST00000510413.5	TSL:1	c.2064T>C	p.His688His	synonymous	Exon 16 of 57	ENSP00000421552.1	P50851-2

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000609 AC: 14 AN: 229744 AF XY: 0.0000401

Gnomad AFR exome AF: 0.000872

Gnomad AMR exome AF: 0.0000345

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 21 AN: 1335238 Hom.: 0 Cov.: 20 AF XY: 0.0000134 AC XY: 9 AN XY: 669698

African (AFR) AF: 0.000635 AC: 19 AN: 29916

American (AMR) AF: 0.00 AC: 0 AN: 39198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24964

East Asian (EAS) AF: 0.00 AC: 0 AN: 37792

South Asian (SAS) AF: 0.00 AC: 0 AN: 78296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5362

European-Non Finnish (NFE) AF: 9.89e-7 AC: 1 AN: 1010982

Other (OTH) AF: 0.0000179 AC: 1 AN: 55772

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74440

African (AFR) AF: 0.000818 AC: 34 AN: 41572

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000199 Hom.: 0

Bravo AF: 0.000215

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Combined immunodeficiency due to LRBA deficiency (1)
-	-	1	LRBA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.9
DANN	Benign	0.68
PhyloP100		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs145198687; hg19: chr4-151817549;