rs6590109

Variant names:

• chr11-124889152-G-A
• rs6590109
• NM_019055.6:c.1949-1312C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ROBO4 Gene-Disease associations (from GenCC):

• aortic valve disease 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ROBO4	NM_019055.6	c.1949-1312C>T		intron_variant	Intron 12 of 17	ENST00000306534.8	NP_061928.4
ROBO4	NM_001441183.1	c.1949-1312C>T		intron_variant	Intron 12 of 17		NP_001428112.1
ROBO4	NM_001301088.2	c.1514-1312C>T		intron_variant	Intron 12 of 17		NP_001288017.1
ROBO4	XM_011542875.2	c.623-1312C>T		intron_variant	Intron 5 of 10		XP_011541177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO4	ENST00000306534.8	c.1949-1312C>T		intron_variant	Intron 12 of 17	1	NM_019055.6	ENSP00000304945.3
ROBO4	ENST00000534407.5	n.1625-1312C>T		intron_variant	Intron 2 of 4	1
ROBO4	ENST00000533054.5	c.1514-1312C>T		intron_variant	Intron 12 of 17	2		ENSP00000437129.1
ROBO4	ENST00000532216.5	n.538-1312C>T		intron_variant	Intron 4 of 7	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

African (AFR) AF: 0.850 AC: 35296 AN: 41518

American (AMR) AF: 0.539 AC: 8242 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3468

East Asian (EAS) AF: 0.388 AC: 2004 AN: 5170

South Asian (SAS) AF: 0.554 AC: 2671 AN: 4824

European-Finnish (FIN) AF: 0.676 AC: 7164 AN: 10604

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 46055 AN: 67994

Other (OTH) AF: 0.689 AC: 1453 AN: 2110

Alfa AF: 0.675 Hom.: 20558

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
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6590109; hg19: chr11-124759048;