rs4606490
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_022370.4(ROBO3):c.1331-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,441,680 control chromosomes in the GnomAD database, including 228,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.58 ( 26556 hom., cov: 32)
Exomes 𝑓: 0.55 ( 201853 hom. )
Consequence
ROBO3
NM_022370.4 intron
NM_022370.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.103
Genes affected
ROBO3 (HGNC:13433): (roundabout guidance receptor 3) This gene is a member of the Roundabout (ROBO) gene family that controls neurite outgrowth, growth cone guidance, and axon fasciculation. ROBO proteins are a subfamily of the immunoglobulin transmembrane receptor superfamily. SLIT proteins 1-3, a family of secreted chemorepellants, are ligands for ROBO proteins and SLIT/ROBO interactions regulate myogenesis, leukocyte migration, kidney morphogenesis, angiogenesis, and vasculogenesis in addition to neurogenesis. This gene, ROBO3, has a putative extracellular domain with five immunoglobulin (Ig)-like loops and three fibronectin (Fn) type III motifs, a transmembrane segment, and a cytoplasmic tail with three conserved signaling motifs: CC0, CC2, and CC3 (CC for conserved cytoplasmic). Unlike other ROBO family members, ROBO3 lacks motif CC1. The ROBO3 gene regulates axonal navigation at the ventral midline of the neural tube. In mouse, loss of Robo3 results in a complete failure of commissural axons to cross the midline throughout the spinal cord and the hindbrain. Mutations ROBO3 result in horizontal gaze palsy with progressive scoliosis (HGPPS); an autosomal recessive disorder characterized by congenital absence of horizontal gaze, progressive scoliosis, and failure of the corticospinal and somatosensory axon tracts to cross the midline in the medulla. [provided by RefSeq, May 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 11-124872835-C-T is Benign according to our data. Variant chr11-124872835-C-T is described in ClinVar as [Benign]. Clinvar id is 1327965.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROBO3 | NM_022370.4 | c.1331-49C>T | intron_variant | ENST00000397801.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROBO3 | ENST00000397801.6 | c.1331-49C>T | intron_variant | 1 | NM_022370.4 | P2 | |||
ROBO3 | ENST00000538940.5 | c.1265-49C>T | intron_variant | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.576 AC: 87455AN: 151878Hom.: 26540 Cov.: 32
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GnomAD3 exomes AF: 0.491 AC: 55080AN: 112096Hom.: 15232 AF XY: 0.490 AC XY: 28028AN XY: 57236
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GnomAD4 exome AF: 0.551 AC: 710705AN: 1289684Hom.: 201853 Cov.: 21 AF XY: 0.547 AC XY: 345755AN XY: 631700
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GnomAD4 genome ? AF: 0.576 AC: 87504AN: 151996Hom.: 26556 Cov.: 32 AF XY: 0.568 AC XY: 42205AN XY: 74286
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Gaze palsy, familial horizontal, with progressive scoliosis 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at