rs72997200
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1
The NM_003721.4(RFXANK):c.213C>T(p.Thr71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,612,860 control chromosomes in the GnomAD database, including 3,386 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
Genomes: 𝑓 0.046 ( 218 hom., cov: 32)
Exomes 𝑓: 0.063 ( 3168 hom. )
Consequence
RFXANK
NM_003721.4 synonymous
NM_003721.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.50
Genes affected
RFXANK (HGNC:9987): (regulatory factor X associated ankyrin containing protein) Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. This protein contains ankyrin repeats involved in protein-protein interactions. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group B. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 19-19196988-C-T is Benign according to our data. Variant chr19-19196988-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 328642.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.
BP7
?
Synonymous conserved (PhyloP=-1.5 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFXANK | NM_003721.4 | c.213C>T | p.Thr71= | synonymous_variant | 4/10 | ENST00000303088.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFXANK | ENST00000303088.9 | c.213C>T | p.Thr71= | synonymous_variant | 4/10 | 1 | NM_003721.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0460 AC: 7001AN: 152156Hom.: 218 Cov.: 32
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GnomAD3 exomes AF: 0.0525 AC: 13109AN: 249892Hom.: 428 AF XY: 0.0551 AC XY: 7453AN XY: 135178
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GnomAD4 exome AF: 0.0628 AC: 91729AN: 1460586Hom.: 3168 Cov.: 33 AF XY: 0.0635 AC XY: 46151AN XY: 726598
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GnomAD4 genome ? AF: 0.0460 AC: 6999AN: 152274Hom.: 218 Cov.: 32 AF XY: 0.0449 AC XY: 3342AN XY: 74464
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
MHC class II deficiency Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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: Frequency - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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