Variant 3-78617615-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

ROBO1 (HGNC:):

ROBO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO1	NM_002941.4 linkuse as main transcript	c.4282+20A>G		intron_variant		ENST00000464233.6	NP_002932.1	Q9Y6N7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6 linkuse as main transcript	c.4282+20A>G		intron_variant		5	NM_002941.4	ENSP00000420321.1		Q9Y6N7-1

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

GnomAD3 exomes

AF:

0.623

AC:

134874

AN:

216406

Hom.:

42581

AF XY:

0.627

AC XY:

73149

AN XY:

116610

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 SAS exome

AF:

0.598

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

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.601

Gnomad4 FIN exome

AF:

0.661

Gnomad4 NFE exome

AF:

0.666

Gnomad4 OTH exome

AF:

0.646

GnomAD4 genome

AF:

0.602

AC:

91418

AN:

151938

Hom.:

28119

Cov.:

AF XY:

0.605

AC XY:

44920

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.465

Gnomad4 AMR

AF:

0.644

Gnomad4 ASJ

AF:

0.685

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.585

Gnomad4 FIN

AF:

0.679

Gnomad4 NFE

AF:

0.660

Gnomad4 OTH

AF:

0.643

Alfa

AF:

0.654

Hom.:

56370

Bravo

AF:

0.592

Asia WGS

AF:

0.551

AC:

1918

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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