Submissions for variant NM_001364905.1(LRBA):c.4159-1G>T

dbSNP: rs1750245794

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centogene AG - the Rare Disease Company	RCV001250246	SCV001424450	likely pathogenic	Severe combined immunodeficiency due to CORO1A deficiency		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002570417	SCV003313054	likely pathogenic	Combined immunodeficiency due to LRBA deficiency	2022-08-05	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change affects an acceptor splice site in intron 25 of the LRBA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LRBA are known to be pathogenic (PMID: 26206937, 26768763). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 973589). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
Baylor Genetics	RCV002570417	SCV003835306	likely pathogenic	Combined immunodeficiency due to LRBA deficiency	2022-07-21	criteria provided, single submitter	clinical testing
National Institute of Immunohaematology, Indian Council of Medical Research	RCV002570417	SCV005402751	likely pathogenic	Combined immunodeficiency due to LRBA deficiency		no assertion criteria provided	research	The variant has not been identified in population databases. The insilico prediction of the variant is damaging