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GeneBe

11-124886510-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_019055.6(ROBO4):c.2748C>T(p.Ser916=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,613,978 control chromosomes in the GnomAD database, including 23,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 4941 hom., cov: 33)
Exomes 𝑓: 0.15 ( 18580 hom. )

Consequence

ROBO4
NM_019055.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.801
Variant links:
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-124886510-G-A is Benign according to our data. Variant chr11-124886510-G-A is described in ClinVar as [Benign]. Clinvar id is 2691020.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.801 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROBO4NM_019055.6 linkuse as main transcriptc.2748C>T p.Ser916= synonymous_variant 16/18 ENST00000306534.8
ROBO4NM_001301088.2 linkuse as main transcriptc.2313C>T p.Ser771= synonymous_variant 16/18
ROBO4XM_006718861.3 linkuse as main transcriptc.2634C>T p.Ser878= synonymous_variant 16/18
ROBO4XM_011542875.2 linkuse as main transcriptc.1422C>T p.Ser474= synonymous_variant 9/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROBO4ENST00000306534.8 linkuse as main transcriptc.2748C>T p.Ser916= synonymous_variant 16/181 NM_019055.6 P1Q8WZ75-1
ENST00000524453.1 linkuse as main transcriptn.674-1209G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.223
AC:
33981
AN:
152060
Hom.:
4926
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.412
Gnomad AMI
AF:
0.223
Gnomad AMR
AF:
0.143
Gnomad ASJ
AF:
0.143
Gnomad EAS
AF:
0.0886
Gnomad SAS
AF:
0.198
Gnomad FIN
AF:
0.242
Gnomad MID
AF:
0.209
Gnomad NFE
AF:
0.141
Gnomad OTH
AF:
0.190
GnomAD3 exomes
AF:
0.164
AC:
41308
AN:
251210
Hom.:
4206
AF XY:
0.163
AC XY:
22078
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.420
Gnomad AMR exome
AF:
0.0951
Gnomad ASJ exome
AF:
0.139
Gnomad EAS exome
AF:
0.0851
Gnomad SAS exome
AF:
0.193
Gnomad FIN exome
AF:
0.230
Gnomad NFE exome
AF:
0.145
Gnomad OTH exome
AF:
0.152
GnomAD4 exome
AF:
0.151
AC:
221139
AN:
1461800
Hom.:
18580
Cov.:
33
AF XY:
0.152
AC XY:
110450
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.422
Gnomad4 AMR exome
AF:
0.0985
Gnomad4 ASJ exome
AF:
0.146
Gnomad4 EAS exome
AF:
0.115
Gnomad4 SAS exome
AF:
0.193
Gnomad4 FIN exome
AF:
0.222
Gnomad4 NFE exome
AF:
0.139
Gnomad4 OTH exome
AF:
0.160
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.224
AC:
34027
AN:
152178
Hom.:
4941
Cov.:
33
AF XY:
0.226
AC XY:
16816
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.413
Gnomad4 AMR
AF:
0.143
Gnomad4 ASJ
AF:
0.143
Gnomad4 EAS
AF:
0.0886
Gnomad4 SAS
AF:
0.197
Gnomad4 FIN
AF:
0.242
Gnomad4 NFE
AF:
0.141
Gnomad4 OTH
AF:
0.189
Alfa
AF:
0.171
Hom.:
1923
Bravo
AF:
0.223
Asia WGS
AF:
0.180
AC:
629
AN:
3478
EpiCase
AF:
0.139
EpiControl
AF:
0.138

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitterclinical testingCHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern OntarioNov 18, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
9.4
Dann
Benign
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7104934; hg19: chr11-124756406; COSMIC: COSV60623508; COSMIC: COSV60623508; API