chr3-78600249-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_002941.4(ROBO1):c.4805G>A(p.Ser1602Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,613,284 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

ROBO1
NM_002941.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.25

Publications

8 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020641416).

BP6

Variant 3-78600249-C-T is Benign according to our data. Variant chr3-78600249-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3718407.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000788 (12/152278) while in subpopulation EAS AF = 0.00232 (12/5180). AF 95% confidence interval is 0.00134. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ROBO1	NM_002941.4	MANE Select	c.4805G>A	p.Ser1602Asn	missense	Exon 30 of 31	NP_002932.1	Q9Y6N7-1
ROBO1	NM_133631.4		c.4670G>A	p.Ser1557Asn	missense	Exon 28 of 29	NP_598334.2	Q9Y6N7-5
ROBO1	NM_001145845.2		c.4505G>A	p.Ser1502Asn	missense	Exon 28 of 29	NP_001139317.1	Q9Y6N7-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.4805G>A	p.Ser1602Asn	missense	Exon 30 of 31	ENSP00000420321.1	Q9Y6N7-1
ROBO1	ENST00000495273.5	TSL:1	c.4670G>A	p.Ser1557Asn	missense	Exon 28 of 29	ENSP00000420637.1	Q9Y6N7-5
ROBO1	ENST00000467549.5	TSL:1	c.4505G>A	p.Ser1502Asn	missense	Exon 28 of 29	ENSP00000417992.1	Q9Y6N7-6

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000141

AC:

AN:

248932

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00184

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000132

AC:

193

AN:

1461006

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

726826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00464

AC:

184

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111334

Other (OTH)

AF:

0.0000663

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00232

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000167

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000199

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.055

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.90

PhyloP100

6.3

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.1

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.027

Polyphen

0.80

Vest4

0.51

MVP

0.78

MPC

0.56

ClinPred

0.12

GERP RS

5.6

Varity_R

0.54

gMVP

0.24

Mutation Taster

=98/2

polymorphism

(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