Genetic Variant ROBO1:c.499+66907G>A (chr3-78871694-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002941.4(ROBO1):c.499+66907G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000337 in 148,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000034 ( 0 hom., cov: 24)

Consequence

ROBO1
NM_002941.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.229

Publications

12 publications found

Variant links:

Genes affected

ROBO1 (HGNC:10249): (roundabout guidance receptor 1) Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The product of this gene is a member of the immunoglobulin gene superfamily and encodes an integral membrane protein that functions in axon guidance and neuronal precursor cell migration. This receptor is activated by SLIT-family proteins, resulting in a repulsive effect on glioma cell guidance in the developing brain. A related gene is located at an adjacent region on chromosome 3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ROBO1 Gene-Disease associations (from GenCC):

neurooculorenal syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
pituitary hormone deficiency, combined or isolated, 8
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
pituitary stalk interruption syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ROBO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ROBO1	NM_002941.4	MANE Select	c.499+66907G>A	intron	N/A	NP_002932.1
ROBO1	NM_133631.4		c.382+66907G>A	intron	N/A	NP_598334.2
ROBO1	NM_001145845.2		c.382+66907G>A	intron	N/A	NP_001139317.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.499+66907G>A	intron	N/A	ENSP00000420321.1
ROBO1	ENST00000495273.5	TSL:1	c.382+66907G>A	intron	N/A	ENSP00000420637.1
ROBO1	ENST00000467549.5	TSL:1	c.382+66907G>A	intron	N/A	ENSP00000417992.1

Frequencies

GnomAD3 genomes

AF:

0.0000337

AC:

AN:

148242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0000337

AC:

AN:

148340

Hom.:

Cov.:

AF XY:

0.0000416

AC XY:

AN XY:

72130

show subpopulations

African (AFR)

AF:

0.0000248

AC:

AN:

40254

American (AMR)

AF:

0.00

AC:

AN:

14842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000199

AC:

AN:

5022

South Asian (SAS)

AF:

0.00

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

67480

Other (OTH)

AF:

0.00

AC:

AN:

2030

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

Genome 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

Alfa

AF:

0.00

Hom.:

21830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Benign

0.88

PhyloP100

-0.23

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over