rs6590109

chr11-124889152-G-A

Variant summary

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

The NM_019055.6(ROBO4):c.1949-1312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,170 control chromosomes in the GnomAD database, including 37,882 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 0.70 (37882 hom., cov: 32)
• Consequence: ROBO4 NM_019055.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO4	NM_019055.6	c.1949-1312C>T		intron_variant		ENST00000306534.8
ROBO4	NM_001301088.2	c.1514-1312C>T		intron_variant
ROBO4	XM_006718861.3	c.1949-1312C>T		intron_variant
ROBO4	XM_011542875.2	c.623-1312C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO4	ENST00000306534.8	c.1949-1312C>T		intron_variant		1	NM_019055.6	P1
ROBO4	ENST00000534407.5	n.1625-1312C>T		intron_variant, non_coding_transcript_variant		1
ROBO4	ENST00000533054.5	c.1514-1312C>T		intron_variant		2
ROBO4	ENST00000532216.5	n.538-1312C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105785 AN: 152052 Hom.: 37858 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.689

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.696 AC: 105855 AN: 152170 Hom.: 37882 Cov.: 32 AF XY: 0.689 AC XY: 51226 AN XY: 74394

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.689

Alfa AF: 0.673 Hom.: 18514

Bravo AF: 0.690

Asia WGS AF: 0.531 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.8
Dann	Benign	0.36

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: rs6590109; hg19: chr11-124759048;