chr11-124891545-G-C

Variant names:

• chr11-124891545-G-C
• rs201492213
• NM_019055.6:c.1702C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019055.6(ROBO4):​c.1702C>G​(p.Arg568Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ROBO4 NM_019055.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20
• Publications: 3 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

ENSG00000254943 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO4	NM_019055.6	c.1702C>G	p.Arg568Gly	missense_variant	Exon 12 of 18	ENST00000306534.8	NP_061928.4
ROBO4	NM_001441183.1	c.1702C>G	p.Arg568Gly	missense_variant	Exon 12 of 18		NP_001428112.1
ROBO4	NM_001301088.2	c.1267C>G	p.Arg423Gly	missense_variant	Exon 12 of 18		NP_001288017.1
ROBO4	XM_011542875.2	c.376C>G	p.Arg126Gly	missense_variant	Exon 5 of 11		XP_011541177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO4	ENST00000306534.8	c.1702C>G	p.Arg568Gly	missense_variant	Exon 12 of 18	1	NM_019055.6	ENSP00000304945.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		3.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		1.0	D;.
Vest4		0.70
MutPred		0.21		Gain of sheet (P = 0.0043);.;
MVP		0.84
MPC		0.50
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.33
gMVP		0.45
Mutation Taster		=92/8	polymorphism

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: rs201492213; hg19: chr11-124761441;