rs11219832

chr11-124897394-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019055.6(ROBO4):c.71-133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 717,918 control chromosomes in the GnomAD database, including 884 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (165 hom., cov: 32)
  • Exomes 𝑓: 0.045 (719 hom.)
• Consequence: ROBO4 NM_019055.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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]

LOC107984406 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO4	NM_019055.6	c.71-133G>A		intron_variant		ENST00000306534.8
LOC107984406	XR_001748429.3	n.334+5262C>T		intron_variant, non_coding_transcript_variant
ROBO4	NM_001301088.2	c.-160+332G>A		intron_variant
ROBO4	XM_006718861.3	c.71-133G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO4	ENST00000306534.8	c.71-133G>A		intron_variant		1	NM_019055.6	P1

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5328 AN: 152150 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.00973

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0448 AC: 25348 AN: 565650 Hom.: 719 AF XY: 0.0436 AC XY: 12530 AN XY: 287488

Gnomad4 AFR exome AF: 0.00867

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.0188

Gnomad4 EAS exome AF: 0.0000994

Gnomad4 SAS exome AF: 0.00589

Gnomad4 FIN exome AF: 0.0572

Gnomad4 NFE exome AF: 0.0553

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.0350 AC: 5329 AN: 152268 Hom.: 165 Cov.: 32 AF XY: 0.0330 AC XY: 2456 AN XY: 74458

Gnomad4 AFR AF: 0.00970

Gnomad4 AMR AF: 0.0237

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0567

Gnomad4 NFE AF: 0.0558

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0460 Hom.: 54

Bravo AF: 0.0324

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.9
Dann	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs11219832; hg19: chr11-124767290;