Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003721.4(RFXANK):c.144G>C(p.Glu48Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,614,068 control chromosomes in the GnomAD database, including 2,728 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
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]
RFXANK Gene-Disease associations (from GenCC):
MHC class II deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0015137196).
BP6
Variant 19-19194090-G-C is Benign according to our data. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-19194090-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 328640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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 -
Dec 10, 2021
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Jan 24, 2024
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -
Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;