chr11-124885135-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_019055.6(ROBO4):c.2907C>T(p.Thr969=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,064 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0064 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 18 hom. )
Consequence
ROBO4
NM_019055.6 synonymous
NM_019055.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.257
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 11-124885135-G-A is Benign according to our data. Variant chr11-124885135-G-A is described in ClinVar as [Benign]. Clinvar id is 717253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.257 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0064 (974/152268) while in subpopulation AFR AF= 0.0225 (936/41550). AF 95% confidence interval is 0.0213. There are 11 homozygotes in gnomad4. There are 438 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 972 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROBO4 | NM_019055.6 | c.2907C>T | p.Thr969= | synonymous_variant | 17/18 | ENST00000306534.8 | |
ROBO4 | NM_001301088.2 | c.2472C>T | p.Thr824= | synonymous_variant | 17/18 | ||
ROBO4 | XM_006718861.3 | c.2793C>T | p.Thr931= | synonymous_variant | 17/18 | ||
ROBO4 | XM_011542875.2 | c.1581C>T | p.Thr527= | synonymous_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROBO4 | ENST00000306534.8 | c.2907C>T | p.Thr969= | synonymous_variant | 17/18 | 1 | NM_019055.6 | P1 | |
ROBO4 | ENST00000534407.5 | n.3114C>T | non_coding_transcript_exon_variant | 4/5 | 1 | ||||
ENST00000524453.1 | n.673+772G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
ROBO4 | ENST00000533054.5 | c.2472C>T | p.Thr824= | synonymous_variant | 17/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00639 AC: 972AN: 152150Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00171 AC: 429AN: 250936Hom.: 10 AF XY: 0.00127 AC XY: 172AN XY: 135732
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GnomAD4 exome AF: 0.000647 AC: 946AN: 1461796Hom.: 18 Cov.: 32 AF XY: 0.000590 AC XY: 429AN XY: 727206
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
ROBO4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 07, 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
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at