Genetic Variant ROBO1:c.88+25243T>C (chr3-79564581-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_002941.4(ROBO1):c.88+25243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,846 control chromosomes in the GnomAD database, including 24,540 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 0.56 ( 24540 hom., cov: 32)

Consequence

ROBO1
NM_002941.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

5 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:

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4 link	c.88+25243T>C		intron_variant	Intron 2 of 30	ENST00000464233.6	NP_002932.1	Q9Y6N7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6 link	c.88+25243T>C		intron_variant	Intron 2 of 30	5	NM_002941.4	ENSP00000420321.1		Q9Y6N7-1
ROBO1	ENST00000492990.1 link	n.88+25243T>C		intron_variant	Intron 1 of 4	3		ENSP00000419915.1		F8WEV8

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84504

AN:

151728

Hom.:

24503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.728

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.541

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

GnomAD4 genome

AF:

0.557

AC:

84596

AN:

151846

Hom.:

24540

Cov.:

AF XY:

0.552

AC XY:

40922

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.728

AC:

30177

AN:

41448

American (AMR)

AF:

0.425

AC:

6464

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

1943

AN:

3470

East Asian (EAS)

AF:

0.427

AC:

2199

AN:

5154

South Asian (SAS)

AF:

0.450

AC:

2166

AN:

4816

European-Finnish (FIN)

AF:

0.482

AC:

5069

AN:

10526

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.513

AC:

34844

AN:

67912

Other (OTH)

AF:

0.544

AC:

1151

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1856

3711

5567

7422

9278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.518

Hom.:

3869

Bravo

AF:

0.560

Asia WGS

AF:

0.456

AC:

1588

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

(source)

DANN

Benign

0.76

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over