chr11-124885038-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_019055.6(ROBO4):c.3001+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,048 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0081 ( 9 hom., cov: 32)
Exomes 𝑓: 0.010 ( 140 hom. )
Consequence
ROBO4
NM_019055.6 splice_donor_region, intron
NM_019055.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00003975
2
Clinical Significance
Conservation
PhyloP100: -0.554
Genes affected
ROBO4 (HGNC:17985): (roundabout guidance receptor 4) Predicted to enable cell-cell adhesion mediator activity. Involved in angiogenesis and establishment of endothelial barrier. Located in extracellular exosome. Implicated in aortic valve disease 3. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 11-124885038-C-T is Benign according to our data. Variant chr11-124885038-C-T is described in ClinVar as [Benign]. Clinvar id is 2642502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00813 (1239/152348) while in subpopulation NFE AF= 0.0124 (844/68032). AF 95% confidence interval is 0.0117. There are 9 homozygotes in gnomad4. There are 539 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1243 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROBO4 | NM_019055.6 | c.3001+3G>A | splice_donor_region_variant, intron_variant | ENST00000306534.8 | |||
ROBO4 | NM_001301088.2 | c.2566+3G>A | splice_donor_region_variant, intron_variant | ||||
ROBO4 | XM_006718861.3 | c.2887+3G>A | splice_donor_region_variant, intron_variant | ||||
ROBO4 | XM_011542875.2 | c.1675+3G>A | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROBO4 | ENST00000306534.8 | c.3001+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_019055.6 | P1 | |||
ENST00000524453.1 | n.673+675C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
ROBO4 | ENST00000534407.5 | n.3208+3G>A | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 1 | |||||
ROBO4 | ENST00000533054.5 | c.2566+3G>A | splice_donor_region_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00817 AC: 1243AN: 152230Hom.: 10 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1243
AN:
152230
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00981 AC: 2465AN: 251236Hom.: 34 AF XY: 0.0104 AC XY: 1419AN XY: 135802
GnomAD3 exomes
AF:
AC:
2465
AN:
251236
Hom.:
AF XY:
AC XY:
1419
AN XY:
135802
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0105 AC: 15314AN: 1461700Hom.: 140 Cov.: 32 AF XY: 0.0105 AC XY: 7621AN XY: 727130
GnomAD4 exome
AF:
AC:
15314
AN:
1461700
Hom.:
Cov.:
32
AF XY:
AC XY:
7621
AN XY:
727130
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00813 AC: 1239AN: 152348Hom.: 9 Cov.: 32 AF XY: 0.00723 AC XY: 539AN XY: 74506
GnomAD4 genome
?
AF:
AC:
1239
AN:
152348
Hom.:
Cov.:
32
AF XY:
AC XY:
539
AN XY:
74506
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3
AN:
3476
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jan 04, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | ROBO4: BP4, BS1, BS2 - |
ROBO4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 16, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at