1-151343685-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001025603.2(RFX5):c.753C>T(p.Leu251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,613,980 control chromosomes in the GnomAD database, including 800,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.98 ( 73019 hom., cov: 30)
Exomes 𝑓: 1.0 ( 727844 hom. )
Consequence
RFX5
NM_001025603.2 synonymous
NM_001025603.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0830
Genes affected
RFX5 (HGNC:9986): (regulatory factor X5) A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920). At least 4 complementation groups have been identified in B-cell lines established from patients with BLS. The molecular defects in complementation groups B, C, and D all lead to a deficiency in RFX, a nuclear protein complex that binds to the X box of MHC-II promoters. The lack of RFX binding activity in complementation group C results from mutations in the RFX5 gene encoding the 75-kD subunit of RFX (Steimle et al., 1995). RFX5 is the fifth member of the growing family of DNA-binding proteins sharing a novel and highly characteristic DNA-binding domain called the RFX motif. Multiple alternatively spliced transcript variants have been found but the full-length natures of only two have been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 1-151343685-G-A is Benign according to our data. Variant chr1-151343685-G-A is described in ClinVar as [Benign]. Clinvar id is 403373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.083 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFX5 | NM_001025603.2 | c.753C>T | p.Leu251= | synonymous_variant | 9/11 | ENST00000452671.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFX5 | ENST00000452671.7 | c.753C>T | p.Leu251= | synonymous_variant | 9/11 | 1 | NM_001025603.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.979 AC: 148891AN: 152122Hom.: 72963 Cov.: 30
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GnomAD3 exomes AF: 0.995 AC: 249239AN: 250606Hom.: 123982 AF XY: 0.996 AC XY: 135023AN XY: 135534
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GnomAD4 exome AF: 0.998 AC: 1458598AN: 1461740Hom.: 727844 Cov.: 55 AF XY: 0.998 AC XY: 725825AN XY: 727154
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GnomAD4 genome ? AF: 0.979 AC: 149006AN: 152240Hom.: 73019 Cov.: 30 AF XY: 0.980 AC XY: 72924AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MHC class II deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at