dbSNP rs12823: ROBO4:n.3407A>T (chr11-124884715-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000534407.5(ROBO4):n.3407A>T 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 0.307 in 724,856 control chromosomes in the GnomAD database, including 38,781 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 0.29 ( 7151 hom., cov: 32)

Exomes 𝑓: 0.31 ( 31630 hom. )

Consequence

ROBO4
ENST00000534407.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0360

Publications

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

ROBO4 links:

ENSG00000254568 (HGNC:):

ENSG00000254568 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ROBO4	NM_019055.6 link	c.*176A>T	3_prime_UTR_variant	Exon 18 of 18	ENST00000306534.8	NP_061928.4	Q8WZ75-1
ROBO4	NM_001441183.1 link	c.*176A>T	3_prime_UTR_variant	Exon 18 of 18		NP_001428112.1
ROBO4	NM_001301088.2 link	c.*176A>T	3_prime_UTR_variant	Exon 18 of 18		NP_001288017.1	Q8WZ75B4DYV8
ROBO4	XM_011542875.2 link	c.*176A>T	3_prime_UTR_variant	Exon 11 of 11		XP_011541177.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ROBO4	ENST00000534407.5 link	n.3407A>T	non_coding_transcript_exon_variant	Exon 5 of 5	1
ROBO4	ENST00000306534.8 link	c.*176A>T	3_prime_UTR_variant	Exon 18 of 18	1	NM_019055.6	ENSP00000304945.3	Q8WZ75-1
ROBO4	ENST00000533054.5 link	c.*176A>T	3_prime_UTR_variant	Exon 18 of 18	2		ENSP00000437129.1	B4DYV8
ENSG00000254568	ENST00000524453.1 link	n.673+352T>A	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44446

AN:

152022

Hom.:

7157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.298

GnomAD4 exome

AF:

0.311

AC:

178352

AN:

572716

Hom.:

31630

Cov.:

AF XY:

0.304

AC XY:

91767

AN XY:

302136

show subpopulations

African (AFR)

AF:

0.220

AC:

3331

AN:

15114

American (AMR)

AF:

0.189

AC:

4807

AN:

25412

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

3981

AN:

15302

East Asian (EAS)

AF:

0.000558

AC:

AN:

34026

South Asian (SAS)

AF:

0.128

AC:

6631

AN:

51914

European-Finnish (FIN)

AF:

0.351

AC:

16024

AN:

45642

Middle Eastern (MID)

AF:

0.266

AC:

633

AN:

2382

European-Non Finnish (NFE)

AF:

0.379

AC:

133508

AN:

352480

Other (OTH)

AF:

0.309

AC:

9418

AN:

30444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5904

11807

17711

23614

29518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.292

AC:

44438

AN:

152140

Hom.:

7151

Cov.:

AF XY:

0.285

AC XY:

21185

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.221

AC:

9186

AN:

41500

American (AMR)

AF:

0.238

AC:

3644

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

929

AN:

3470

East Asian (EAS)

AF:

0.00232

AC:

AN:

5172

South Asian (SAS)

AF:

0.126

AC:

610

AN:

4828

European-Finnish (FIN)

AF:

0.341

AC:

3612

AN:

10582

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25495

AN:

67982

Other (OTH)

AF:

0.295

AC:

623

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1600

3200

4801

6401

8001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.337

Hom.:

1209

Bravo

AF:

0.282

Asia WGS

AF:

0.0660

AC:

230

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

(source)

DANN

Benign

0.75

PhyloP100

-0.036

Mutation Taster

=100/0

polymorphism (auto)

(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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rs12823

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over