ENST00000534407.5:n.153T>C

Variant names:

• chr11-124892873-A-G
• rs11219831
• ENST00000534407.5:n.153T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000534407.5(ROBO4):​n.153T>C variant causes a non coding transcript exon 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 ENST00000534407.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
ROBO4	NM_019055.6	c.1547+815T>C		intron_variant	Intron 10 of 17	ENST00000306534.8	NP_061928.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO4	ENST00000306534.8	c.1547+815T>C		intron_variant	Intron 10 of 17	1	NM_019055.6	ENSP00000304945.3

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

African (AFR) AF: 0.00 AC: 0 AN: 18

American (AMR) AF: 0.100 AC: 1 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.100 AC: 2 AN: 20

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.102 AC: 31 AN: 304

Other (OTH) AF: 0.233 AC: 7 AN: 30

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

African (AFR) AF: 0.0296 AC: 1231 AN: 41574

American (AMR) AF: 0.118 AC: 1808 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3466

East Asian (EAS) AF: 0.294 AC: 1521 AN: 5168

South Asian (SAS) AF: 0.227 AC: 1093 AN: 4822

European-Finnish (FIN) AF: 0.0925 AC: 980 AN: 10594

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.146 AC: 9908 AN: 68010

Other (OTH) AF: 0.139 AC: 294 AN: 2116

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
PhyloP100		-0.070
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: rs11219831; hg19: chr11-124762769;