4-150310219-T-C

Variant names:

• chr4-150310219-T-C
• rs1813134
• NM_001364905.1:c.7849+10A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001364905.1(LRBA):​c.7849+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,594,122 control chromosomes in the GnomAD database, including 340,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29855 hom., cov: 32)
  • Exomes 𝑓: 0.65 (310566 hom.)
• Consequence: LRBA NM_001364905.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: 0.645
• Publications: 14 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 4-150310219-T-C is Benign according to our data. Variant chr4-150310219-T-C is described in ClinVar as Benign. ClinVar VariationId is 403049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

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.7849+10A>G		intron	N/A	NP_001351834.1	A0A494C1L5
	LRBA	NM_001440430.1		c.7897+10A>G		intron	N/A	NP_001427359.1
	LRBA	NM_006726.5		c.7882+10A>G		intron	N/A	NP_006717.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRBA	ENST00000651943.2	MANE Select	c.7849+10A>G		intron	N/A	ENSP00000498582.2	A0A494C1L5
	LRBA	ENST00000357115.9	TSL:1	c.7882+10A>G		intron	N/A	ENSP00000349629.3	P50851-1
	LRBA	ENST00000510413.5	TSL:1	c.7849+10A>G		intron	N/A	ENSP00000421552.1	P50851-2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94532 AN: 151844 Hom.: 29850 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.624

GnomAD2 exomes AF: 0.596 AC: 148419 AN: 248818 AF XY: 0.601

Gnomad AFR exome AF: 0.579

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.681

Gnomad EAS exome AF: 0.432

Gnomad FIN exome AF: 0.674

Gnomad NFE exome AF: 0.687

Gnomad OTH exome AF: 0.613

GnomAD4 exome AF: 0.651 AC: 938915 AN: 1442160 Hom.: 310566 Cov.: 26 AF XY: 0.648 AC XY: 465333 AN XY: 718182

African (AFR) AF: 0.580 AC: 19168 AN: 33028

American (AMR) AF: 0.435 AC: 19295 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 17595 AN: 25860

East Asian (EAS) AF: 0.457 AC: 18066 AN: 39540

South Asian (SAS) AF: 0.484 AC: 41242 AN: 85150

European-Finnish (FIN) AF: 0.681 AC: 36063 AN: 52958

Middle Eastern (MID) AF: 0.630 AC: 3506 AN: 5566

European-Non Finnish (NFE) AF: 0.681 AC: 746506 AN: 1096050

Other (OTH) AF: 0.628 AC: 37474 AN: 59672

GnomAD4 genome AF: 0.622 AC: 94572 AN: 151962 Hom.: 29855 Cov.: 32 AF XY: 0.617 AC XY: 45811 AN XY: 74256

African (AFR) AF: 0.575 AC: 23856 AN: 41468

American (AMR) AF: 0.536 AC: 8173 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2316 AN: 3466

East Asian (EAS) AF: 0.434 AC: 2237 AN: 5160

South Asian (SAS) AF: 0.472 AC: 2268 AN: 4804

European-Finnish (FIN) AF: 0.675 AC: 7124 AN: 10550

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46517 AN: 67956

Other (OTH) AF: 0.623 AC: 1311 AN: 2106

Alfa AF: 0.658 Hom.: 125975

Bravo AF: 0.607

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Combined immunodeficiency due to LRBA deficiency (2)
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.65
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: rs1813134; hg19: chr4-151231371; COSMIC: COSV63956175; COSMIC: COSV63956175;