Genetic Variant NM_019055.6:c.1547+815T>C (chr11-124892873-A-G) – 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.1547+815T>C variant causes a intron 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
NM_019055.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0700

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:

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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 (EAS) allele frequency at 95% confidence interval = 0.282 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.1547+815T>C	intron	N/A	NP_061928.4
ROBO4	NM_001441183.1		c.1547+815T>C	intron	N/A	NP_001428112.1
ROBO4	NM_001301088.2		c.1112+815T>C	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.1547+815T>C	intron	N/A	ENSP00000304945.3	Q8WZ75-1
ROBO4	ENST00000534407.5	TSL:1	n.153T>C	non_coding_transcript_exon	Exon 1 of 5
ROBO4	ENST00000877825.1		c.1547+815T>C	intron	N/A	ENSP00000547884.1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17594

AN:

152132

Hom.:

1366

Cov.:

show subpopulations

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:

AN:

394

Hom.:

Cov.:

AF XY:

0.110

AC XY:

AN XY:

290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.102

AC:

AN:

304

Other (OTH)

AF:

0.233

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.115

AC:

17584

AN:

152250

Hom.:

1365

Cov.:

AF XY:

0.116

AC XY:

8652

AN XY:

74420

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.146

AC:

9908

AN:

68010

Other (OTH)

AF:

0.139

AC:

294

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

786

1573

2359

3146

3932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.0746

Hom.:

100

Bravo

AF:

0.112

Asia WGS

AF:

0.264

AC:

918

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

(source)

DANN

Benign

0.73

PhyloP100

-0.070

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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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