NM_002941.4:c.4283-6C>T

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.4283-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,543,268 control chromosomes in the GnomAD database, including 129,111 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 0.37 ( 11037 hom., cov: 29)

Exomes 𝑓: 0.41 ( 118074 hom. )

Consequence

ROBO1
NM_002941.4 splice_region, intron

Scores

Splicing: ADA: 0.00003322

Clinical Significance

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

Conservation

PhyloP100: -0.360

Publications

13 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=-0.84).

BP6

Variant 3-78614806-G-A is Benign according to our data. Variant chr3-78614806-G-A is described in ClinVar as Benign. ClinVar VariationId is 1642377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4 link	c.4283-6C>T		splice_region_variant, intron_variant	Intron 27 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.4283-6C>T		splice_region_variant, intron_variant	Intron 27 of 30	5	NM_002941.4	ENSP00000420321.1		Q9Y6N7-1

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

54878

AN:

147056

Hom.:

11036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.400

GnomAD2 exomes

AF:

0.454

AC:

80681

AN:

177654

AF XY:

0.453

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.441

Gnomad OTH exome

AF:

0.450

GnomAD4 exome

AF:

0.410

AC:

571734

AN:

1396124

Hom.:

118074

Cov.:

AF XY:

0.411

AC XY:

284078

AN XY:

691988

show subpopulations

African (AFR)

AF:

0.205

AC:

6275

AN:

30636

American (AMR)

AF:

0.562

AC:

20003

AN:

35584

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

11016

AN:

24424

East Asian (EAS)

AF:

0.291

AC:

10974

AN:

37694

South Asian (SAS)

AF:

0.432

AC:

33017

AN:

76468

European-Finnish (FIN)

AF:

0.465

AC:

22089

AN:

47486

Middle Eastern (MID)

AF:

0.413

AC:

2272

AN:

5496

European-Non Finnish (NFE)

AF:

0.410

AC:

442732

AN:

1080834

Other (OTH)

AF:

0.406

AC:

23356

AN:

57502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

14376

28752

43129

57505

71881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13830

27660

41490

55320

69150

<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:

0.373

AC:

54888

AN:

147144

Hom.:

11037

Cov.:

AF XY:

0.380

AC XY:

27149

AN XY:

71536

show subpopulations

African (AFR)

AF:

0.212

AC:

8338

AN:

39408

American (AMR)

AF:

0.501

AC:

7492

AN:

14964

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1525

AN:

3426

East Asian (EAS)

AF:

0.325

AC:

1623

AN:

4996

South Asian (SAS)

AF:

0.434

AC:

2028

AN:

4672

European-Finnish (FIN)

AF:

0.487

AC:

4606

AN:

9452

Middle Eastern (MID)

AF:

0.418

AC:

118

AN:

282

European-Non Finnish (NFE)

AF:

0.416

AC:

27844

AN:

66990

Other (OTH)

AF:

0.399

AC:

821

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1614

3228

4841

6455

8069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.400

Hom.:

52695

Bravo

AF:

0.361

Asia WGS

AF:

0.366

AC:

1260

AN:

3442

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.44

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.012

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over