Genetic Variant NM_019055.6:c.1037-79G>A (chr11-124895272-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.1037-79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,247,086 control chromosomes in the GnomAD database, including 16,735 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 0.16 ( 1999 hom., cov: 32)

Exomes 𝑓: 0.16 ( 14736 hom. )

Consequence

ROBO4
NM_019055.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0850

Publications

6 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:

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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ROBO4	NM_019055.6 link	c.1037-79G>A	intron_variant	Intron 6 of 17	ENST00000306534.8	NP_061928.4	Q8WZ75-1
ROBO4	NM_001441183.1 link	c.1037-79G>A	intron_variant	Intron 6 of 17		NP_001428112.1
ROBO4	NM_001301088.2 link	c.602-79G>A	intron_variant	Intron 6 of 17		NP_001288017.1	Q8WZ75B4DYV8
LOC107984406	XR_001748429.3 link	n.334+3140C>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO4	ENST00000306534.8 link	c.1037-79G>A		intron_variant	Intron 6 of 17	1	NM_019055.6	ENSP00000304945.3		Q8WZ75-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24072

AN:

151854

Hom.:

1999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.146

GnomAD4 exome

AF:

0.160

AC:

175575

AN:

1095114

Hom.:

14736

Cov.:

AF XY:

0.162

AC XY:

90152

AN XY:

556906

show subpopulations

African (AFR)

AF:

0.143

AC:

3752

AN:

26204

American (AMR)

AF:

0.0882

AC:

3322

AN:

37684

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

2774

AN:

22502

East Asian (EAS)

AF:

0.161

AC:

5930

AN:

36850

South Asian (SAS)

AF:

0.207

AC:

15607

AN:

75316

European-Finnish (FIN)

AF:

0.266

AC:

13552

AN:

50978

Middle Eastern (MID)

AF:

0.168

AC:

635

AN:

3788

European-Non Finnish (NFE)

AF:

0.154

AC:

122570

AN:

793836

Other (OTH)

AF:

0.155

AC:

7433

AN:

47956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7936

15872

23807

31743

39679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3878

7756

11634

15512

19390

<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:

0.158

AC:

24084

AN:

151972

Hom.:

1999

Cov.:

AF XY:

0.165

AC XY:

12262

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.144

AC:

5988

AN:

41458

American (AMR)

AF:

0.121

AC:

1842

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

418

AN:

3464

East Asian (EAS)

AF:

0.133

AC:

683

AN:

5150

South Asian (SAS)

AF:

0.211

AC:

1013

AN:

4800

European-Finnish (FIN)

AF:

0.287

AC:

3037

AN:

10564

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10546

AN:

67940

Other (OTH)

AF:

0.146

AC:

308

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1040

2079

3119

4158

5198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.145

Hom.:

2821

Bravo

AF:

0.143

Asia WGS

AF:

0.188

AC:

652

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.6

(source)

DANN

Benign

0.90

PhyloP100

-0.085

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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