dbSNP rs11219832: ROBO4:c.71-133G>A (chr11-124897394-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019055.6(ROBO4):c.71-133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 717,918 control chromosomes in the GnomAD database, including 884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.035 ( 165 hom., cov: 32)

Exomes 𝑓: 0.045 ( 719 hom. )

Consequence

ROBO4
NM_019055.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.635

Publications

4 publications found

Variant links:

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, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ROBO4 links:

ENSG00000254943 (HGNC:):

ENSG00000254943 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019055.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROBO4	NM_019055.6	MANE Select	c.71-133G>A	intron	N/A	NP_061928.4
ROBO4	NM_001441183.1		c.71-133G>A	intron	N/A	NP_001428112.1
ROBO4	NM_001301088.2		c.-160+332G>A	intron	N/A	NP_001288017.1	B4DYV8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROBO4	ENST00000306534.8	TSL:1 MANE Select	c.71-133G>A	intron	N/A	ENSP00000304945.3	Q8WZ75-1
ROBO4	ENST00000877825.1		c.71-133G>A	intron	N/A	ENSP00000547884.1
ROBO4	ENST00000877820.1		c.71-133G>A	intron	N/A	ENSP00000547879.1

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5328

AN:

152150

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00973

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.0567

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0558

Gnomad OTH

AF:

0.0320

GnomAD4 exome

AF:

0.0448

AC:

25348

AN:

565650

Hom.:

719

AF XY:

0.0436

AC XY:

12530

AN XY:

287488

show subpopulations

African (AFR)

AF:

0.00867

AC:

127

AN:

14652

American (AMR)

AF:

0.0236

AC:

382

AN:

16184

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

264

AN:

14054

East Asian (EAS)

AF:

0.0000994

AC:

AN:

30192

South Asian (SAS)

AF:

0.00589

AC:

223

AN:

37892

European-Finnish (FIN)

AF:

0.0572

AC:

1647

AN:

28806

Middle Eastern (MID)

AF:

0.00182

AC:

AN:

3850

European-Non Finnish (NFE)

AF:

0.0553

AC:

21581

AN:

390454

Other (OTH)

AF:

0.0377

AC:

1114

AN:

29566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1284

2567

3851

5134

6418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0350

AC:

5329

AN:

152268

Hom.:

165

Cov.:

AF XY:

0.0330

AC XY:

2456

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00970

AC:

403

AN:

41560

American (AMR)

AF:

0.0237

AC:

363

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00684

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0567

AC:

601

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0558

AC:

3797

AN:

68002

Other (OTH)

AF:

0.0317

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

256

511

767

1022

1278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0510

Hom.:

333

Bravo

AF:

0.0324

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.9

(source)

DANN

Benign

0.32

PhyloP100

0.64

PromoterAI

0.030

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over