Variant chr3-78627317-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002941.4(ROBO1):c.3875+4T>C variant causes a splice donor 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. 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_donor_region, intron

Scores

Splicing: ADA: 0.00001445

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 1542355.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4 linkuse as main transcript	c.3875+4T>C		splice_donor_region_variant, intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6 linkuse as main transcript	c.3875+4T>C		splice_donor_region_variant, intron_variant		5	NM_002941.4	P3	Q9Y6N7-1

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

GnomAD3 exomes

AF:

0.966

AC:

236571

AN:

244810

Hom.:

114342

AF XY:

0.964

AC XY:

127853

AN XY:

132652

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 SAS exome

AF:

0.930

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

Gnomad4 AFR exome

AF:

0.981

Gnomad4 AMR exome

AF:

0.984

Gnomad4 ASJ exome

AF:

0.982

Gnomad4 EAS exome

AF:

0.996

Gnomad4 SAS exome

AF:

0.931

Gnomad4 FIN exome

AF:

0.964

Gnomad4 NFE exome

AF:

0.965

Gnomad4 OTH exome

AF:

0.967

GnomAD4 genome

AF:

0.970

AC:

147686

AN:

152282

Hom.:

71634

Cov.:

AF XY:

0.970

AC XY:

72187

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.978

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.982

Gnomad4 EAS

AF:

0.991

Gnomad4 SAS

AF:

0.925

Gnomad4 FIN

AF:

0.966

Gnomad4 NFE

AF:

0.964

Gnomad4 OTH

AF:

0.975

Alfa

AF:

0.967

Hom.:

45133

Bravo

AF:

0.973

Asia WGS

AF:

0.956

AC:

3325

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0010

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over