11-124892873-A-G

Position:

• chr11-124892873-A-G

Variant summary

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

The NM_019055.6(ROBO4):​c.1547+815T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,644 control chromosomes in the GnomAD database, including 1,369 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 0.12 (1365 hom., cov: 33)
  • Exomes 𝑓: 0.11 (4 hom.)
• Consequence: ROBO4 NM_019055.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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 (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO4	NM_019055.6	c.1547+815T>C		intron_variant		ENST00000306534.8
LOC107984406	XR_001748429.3	n.334+741A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO4	ENST00000306534.8	c.1547+815T>C		intron_variant		1	NM_019055.6	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17594 AN: 152132 Hom.: 1366 Cov.: 33

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.112 AC: 44 AN: 394 Hom.: 4 Cov.: 0 AF XY: 0.110 AC XY: 32 AN XY: 290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.115 AC: 17584 AN: 152250 Hom.: 1365 Cov.: 33 AF XY: 0.116 AC XY: 8652 AN XY: 74420

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0925

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0746 Hom.: 100

Bravo AF: 0.112

Asia WGS AF: 0.264 AC: 918 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	1.5
DANN	Benign	0.73

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: rs11219831; hg19: chr11-124762769;