3-78627317-A-G

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.3875+4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 1,611,048 control chromosomes in the GnomAD database, including 751,405 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71634 hom., cov: 32)

Exomes 𝑓: 0.97 ( 679771 hom. )

Consequence

ROBO1
NM_002941.4 splice_region, intron

Scores

Splicing: ADA: 0.00001445

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.02

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-78627317-A-G is Benign according to our data. Variant chr3-78627317-A-G is described in ClinVar as Benign. ClinVar VariationId is 1542355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 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
ROBO1	NM_002941.4	MANE Select	c.3875+4T>C	splice_region intron	N/A	NP_002932.1
ROBO1	NM_133631.4		c.3740+4T>C	splice_region intron	N/A	NP_598334.2
ROBO1	NM_001145845.2		c.3575+4T>C	splice_region intron	N/A	NP_001139317.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.3875+4T>C	splice_region intron	N/A	ENSP00000420321.1
ROBO1	ENST00000495273.5	TSL:1	c.3740+4T>C	splice_region intron	N/A	ENSP00000420637.1
ROBO1	ENST00000467549.5	TSL:1	c.3575+4T>C	splice_region intron	N/A	ENSP00000417992.1

Frequencies

GnomAD3 genomes

AF:

0.970

AC:

147570

AN:

152164

Hom.:

71577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.978

Gnomad AMI

AF:

0.992

Gnomad AMR

AF:

0.976

Gnomad ASJ

AF:

0.982

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.925

Gnomad FIN

AF:

0.966

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.964

Gnomad OTH

AF:

0.976

GnomAD2 exomes

AF:

0.966

AC:

236571

AN:

244810

AF XY:

0.964

show subpopulations

Gnomad AFR exome

AF:

0.979

Gnomad AMR exome

AF:

0.984

Gnomad ASJ exome

AF:

0.982

Gnomad EAS exome

AF:

0.992

Gnomad FIN exome

AF:

0.964

Gnomad NFE exome

AF:

0.964

Gnomad OTH exome

AF:

0.967

GnomAD4 exome

AF:

0.965

AC:

1408085

AN:

1458766

Hom.:

679771

Cov.:

AF XY:

0.964

AC XY:

699262

AN XY:

725310

show subpopulations

African (AFR)

AF:

0.981

AC:

32820

AN:

33448

American (AMR)

AF:

0.984

AC:

43725

AN:

44438

Ashkenazi Jewish (ASJ)

AF:

0.982

AC:

25544

AN:

26016

East Asian (EAS)

AF:

0.996

AC:

39345

AN:

39522

South Asian (SAS)

AF:

0.931

AC:

79832

AN:

85726

European-Finnish (FIN)

AF:

0.964

AC:

51377

AN:

53298

Middle Eastern (MID)

AF:

0.953

AC:

5485

AN:

5756

European-Non Finnish (NFE)

AF:

0.965

AC:

1071711

AN:

1110324

Other (OTH)

AF:

0.967

AC:

58246

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2319

4638

6958

9277

11596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21626

43252

64878

86504

108130

<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:

0.970

AC:

147686

AN:

152282

Hom.:

71634

Cov.:

AF XY:

0.970

AC XY:

72187

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.978

AC:

40665

AN:

41564

American (AMR)

AF:

0.976

AC:

14926

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.982

AC:

3408

AN:

3472

East Asian (EAS)

AF:

0.991

AC:

5118

AN:

5162

South Asian (SAS)

AF:

0.925

AC:

4464

AN:

4824

European-Finnish (FIN)

AF:

0.966

AC:

10257

AN:

10622

Middle Eastern (MID)

AF:

0.966

AC:

284

AN:

294

European-Non Finnish (NFE)

AF:

0.964

AC:

65596

AN:

68024

Other (OTH)

AF:

0.975

AC:

2063

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

229

457

686

914

1143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.968

Hom.:

50572

Bravo

AF:

0.973

Asia WGS

AF:

0.956

AC:

3325

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0010

(source)

DANN

Benign

0.46

PhyloP100

-2.0

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

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over