21-33325081-CG-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000629.3(IFNAR1):c.27delG(p.Thr10ProfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000629.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000415 AC: 1AN: 240692Hom.: 0 AF XY: 0.00000762 AC XY: 1AN XY: 131166
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457772Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 724994
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Thr10Profs*2) in the IFNAR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFNAR1 are known to be pathogenic (PMID: 31270247, 32960813). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with IFNAR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2050663). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at