rs17027133
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001364905.1(LRBA):āc.5030A>Gā(p.Asn1677Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000873 in 1,614,168 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N1677N) has been classified as Likely benign.
Frequency
Consequence
NM_001364905.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.5030A>G | p.Asn1677Ser | missense_variant | 30/57 | ENST00000651943.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.5030A>G | p.Asn1677Ser | missense_variant | 30/57 | NM_001364905.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00333 AC: 507AN: 152224Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00113 AC: 284AN: 251350Hom.: 0 AF XY: 0.000994 AC XY: 135AN XY: 135836
GnomAD4 exome AF: 0.000616 AC: 901AN: 1461826Hom.: 1 Cov.: 32 AF XY: 0.000627 AC XY: 456AN XY: 727214
GnomAD4 genome AF: 0.00333 AC: 508AN: 152342Hom.: 2 Cov.: 32 AF XY: 0.00297 AC XY: 221AN XY: 74504
ClinVar
Submissions by phenotype
Combined immunodeficiency due to LRBA deficiency Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Oct 02, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology | May 17, 2022 | The c.5030A>G variant is present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and Indian Exome Database, at a low frequency. The variant is also present in our in-house exome database. The variant was previously reported to ClinVar (Accession: VCV000540408.9) with conflicitng interpretations of pathogenicity (Uncertain significane/benign) in association with combined immunodeficiency due to LRBA deficiency. In-silico pathogenicity prediction programs like SIFT, PolyPhen-2, MutationTaster2, CADD predicted this variant to be likely deleterious, however these predictions were not confirmed by any published functional studies. - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 31, 2017 | Although the p.Asn1677Ser variant (rs17027133) has not been reported in the medical literature, it is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.99% in the African population (identified in 238 out of 24,032 chromosomes). The asparagine at codon 1677 is moderately conserved considering 13 species (Alamut software v2.10.0), and computational analyses predict that this variant does affect the structure/function of the LRBA protein (SIFT: damaging, PolyPhen2: probably damaging, MutationTaster: disease causing). However, based on the available information, the clinical significance of the p.Asn1677Ser variant cannot be determined with certainty. - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | LRBA: BS1, BS2 - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 04, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 30, 2017 | - - |
LRBA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 09, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at