19-19192475-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003721.4(RFXANK):c.-229C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 357,878 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.035 ( 162 hom., cov: 32)
Exomes 𝑓: 0.038 ( 257 hom. )
Consequence
RFXANK
NM_003721.4 5_prime_UTR
NM_003721.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.797
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 19-19192475-C-T is Benign according to our data. Variant chr19-19192475-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 328638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFXANK | NM_003721.4 | c.-229C>T | 5_prime_UTR_variant | 1/10 | ENST00000303088.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFXANK | ENST00000303088.9 | c.-229C>T | 5_prime_UTR_variant | 1/10 | 1 | NM_003721.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0348 AC: 5293AN: 152156Hom.: 161 Cov.: 32
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GnomAD4 exome AF: 0.0384 AC: 7893AN: 205604Hom.: 257 Cov.: 0 AF XY: 0.0387 AC XY: 4185AN XY: 108142
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GnomAD4 genome AF: 0.0348 AC: 5297AN: 152274Hom.: 162 Cov.: 32 AF XY: 0.0360 AC XY: 2682AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MHC class II deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at