ClinVar Miner

Submissions for variant NM_001364905.1(LRBA):c.4618A>C (p.Ile1540Leu)

gnomAD frequency: 0.00001  dbSNP: rs550389924
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001332812 SCV001525234 uncertain significance Combined immunodeficiency due to LRBA deficiency 2019-10-30 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV003346480 SCV004060598 uncertain significance Inborn genetic diseases 2023-07-25 criteria provided, single submitter clinical testing The c.4618A>C (p.I1540L) alteration is located in exon 29 (coding exon 28) of the LRBA gene. This alteration results from a A to C substitution at nucleotide position 4618, causing the isoleucine (I) at amino acid position 1540 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001332812 SCV004528855 uncertain significance Combined immunodeficiency due to LRBA deficiency 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1540 of the LRBA protein (p.Ile1540Leu). 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: 1031077). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LRBA protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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