rs201405662
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001023570.4(IQCB1):c.214C>T(p.Arg72Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,612,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001023570.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQCB1 | NM_001023570.4 | c.214C>T | p.Arg72Ter | stop_gained | 4/15 | ENST00000310864.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQCB1 | ENST00000310864.11 | c.214C>T | p.Arg72Ter | stop_gained | 4/15 | 1 | NM_001023570.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251296Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135806
GnomAD4 exome AF: 0.0000917 AC: 134AN: 1460720Hom.: 0 Cov.: 30 AF XY: 0.0000936 AC XY: 68AN XY: 726750
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74402
ClinVar
Submissions by phenotype
Senior-Loken syndrome 5 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 11, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 27, 2022 | - - |
Leber congenital amaurosis Pathogenic:2
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | DBGen Ocular Genomics | Jun 18, 2021 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 05, 2016 | - - |
Nephronophthisis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2023 | This sequence change creates a premature translational stop signal (p.Arg72*) in the IQCB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IQCB1 are known to be pathogenic (PMID: 15723066, 21901789, 23559409, 28041643). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 285623). This premature translational stop signal has been observed in individual(s) with early onset retinal disease (PMID: 28041643, 28559085). This variant is present in population databases (rs201405662, gnomAD 0.008%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at