rs145812385
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001364905.1(LRBA):c.1713C>T(p.His571His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000939 in 1,613,584 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001364905.1 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRBA | NM_001364905.1 | c.1713C>T | p.His571His | synonymous_variant | Exon 13 of 57 | ENST00000651943.2 | NP_001351834.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRBA | ENST00000651943.2 | c.1713C>T | p.His571His | synonymous_variant | Exon 13 of 57 | NM_001364905.1 | ENSP00000498582.2 |
Frequencies
GnomAD3 genomes AF: 0.000953 AC: 145AN: 152150Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000610 AC: 153AN: 250826Hom.: 0 AF XY: 0.000635 AC XY: 86AN XY: 135536
GnomAD4 exome AF: 0.000938 AC: 1370AN: 1461316Hom.: 2 Cov.: 30 AF XY: 0.000913 AC XY: 664AN XY: 726950
GnomAD4 genome AF: 0.000952 AC: 145AN: 152268Hom.: 0 Cov.: 31 AF XY: 0.000779 AC XY: 58AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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The p.His571His variant (rs145812385) does not alter the amino acid sequence of the LRBA protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site (Alamut v2.10). This variant has not been reported in association with immunodeficiency in medical literature or in gene specific variation databases. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.01 percent in the European Non-Finnish population (identified on 130 out of 126,186 chromosomes), and has been reported to the ClinVar database (Variation ID: 284747). Based on these observations, the p.His571His variant is likely to be benign. -
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not specified Benign:1
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Combined immunodeficiency due to LRBA deficiency Benign:1
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LRBA-related disorder Benign:1
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