chr3-78617615-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002941.4(ROBO1):c.4282+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,569,684 control chromosomes in the GnomAD database, including 333,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28119 hom., cov: 32)

Exomes 𝑓: 0.65 ( 305003 hom. )

Consequence

ROBO1
NM_002941.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0260

Publications

9 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
pituitary hormone deficiency, combined or isolated, 8
Inheritance: AD, SD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
pituitary stalk interruption syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital heart disease
Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen
nystagmus, congenital, autosomal recessive
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ROBO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-78617615-T-C is Benign according to our data. Variant chr3-78617615-T-C is described in ClinVar as Benign. ClinVar VariationId is 1241025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

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	UniProt
ROBO1	NM_002941.4	MANE Select	c.4282+20A>G	intron	N/A	NP_002932.1	Q9Y6N7-1
ROBO1	NM_133631.4		c.4147+20A>G	intron	N/A	NP_598334.2	Q9Y6N7-5
ROBO1	NM_001145845.2		c.3982+20A>G	intron	N/A	NP_001139317.1	Q9Y6N7-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.4282+20A>G	intron	N/A	ENSP00000420321.1	Q9Y6N7-1
ROBO1	ENST00000495273.5	TSL:1	c.4147+20A>G	intron	N/A	ENSP00000420637.1	Q9Y6N7-5
ROBO1	ENST00000467549.5	TSL:1	c.3982+20A>G	intron	N/A	ENSP00000417992.1	Q9Y6N7-6

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91382

AN:

151822

Hom.:

28115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.679

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.644

GnomAD2 exomes

AF:

0.623

AC:

134874

AN:

216406

AF XY:

0.627

show subpopulations

Gnomad AFR exome

AF:

0.464

Gnomad AMR exome

AF:

0.614

Gnomad ASJ exome

AF:

0.692

Gnomad EAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.670

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.654

AC:

927098

AN:

1417746

Hom.:

305003

Cov.:

AF XY:

0.653

AC XY:

457453

AN XY:

700548

show subpopulations

African (AFR)

AF:

0.464

AC:

14908

AN:

32128

American (AMR)

AF:

0.618

AC:

24003

AN:

38826

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

15906

AN:

22958

East Asian (EAS)

AF:

0.577

AC:

22692

AN:

39298

South Asian (SAS)

AF:

0.601

AC:

47630

AN:

79202

European-Finnish (FIN)

AF:

0.661

AC:

34314

AN:

51942

Middle Eastern (MID)

AF:

0.694

AC:

3784

AN:

5450

European-Non Finnish (NFE)

AF:

0.666

AC:

726248

AN:

1089686

Other (OTH)

AF:

0.646

AC:

37613

AN:

58256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

16668

33336

50005

66673

83341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19110

38220

57330

76440

95550

<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:

0.602

AC:

91418

AN:

151938

Hom.:

28119

Cov.:

AF XY:

0.605

AC XY:

44920

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.465

AC:

19269

AN:

41404

American (AMR)

AF:

0.644

AC:

9838

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

2380

AN:

3472

East Asian (EAS)

AF:

0.557

AC:

2860

AN:

5132

South Asian (SAS)

AF:

0.585

AC:

2819

AN:

4822

European-Finnish (FIN)

AF:

0.679

AC:

7174

AN:

10558

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.660

AC:

44867

AN:

67974

Other (OTH)

AF:

0.643

AC:

1352

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1821

3642

5463

7284

9105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.642

Hom.:

126893

Bravo

AF:

0.592

Asia WGS

AF:

0.551

AC:

1918

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

(source)

DANN

Benign

0.50

PhyloP100

0.026

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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