rs1554639173
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001190737.2(NFIB):c.1063_1076del(p.Ile355SerfsTer48) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
NFIB
NM_001190737.2 frameshift, splice_region
NM_001190737.2 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.13
Genes affected
NFIB (HGNC:7785): (nuclear factor I B) Enables DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and transcription regulator inhibitor activity. Involved in brain development; negative regulation of DNA binding activity; and regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-14120608-AGTTCGAGTTGAGAT-A is Pathogenic according to our data. Variant chr9-14120608-AGTTCGAGTTGAGAT-A is described in ClinVar as [Pathogenic]. Clinvar id is 560029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-14120608-AGTTCGAGTTGAGAT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFIB | NM_001190737.2 | c.1063_1076del | p.Ile355SerfsTer48 | frameshift_variant, splice_region_variant | 8/11 | ENST00000380953.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFIB | ENST00000380953.6 | c.1063_1076del | p.Ile355SerfsTer48 | frameshift_variant, splice_region_variant | 8/11 | 1 | NM_001190737.2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Macrocephaly;C3714756:Intellectual disability Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Department of Human Genetics, University Hospital Magdeburg | - | - - |
Macrocephaly, acquired, with impaired intellectual development Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 23, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at