Variant 3-78606773-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002941.4(ROBO1):c.4704A>C(p.Ala1568=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,932 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 24 hom., cov: 32)

Exomes 𝑓: 0.014 ( 210 hom. )

Consequence

ROBO1
NM_002941.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.544

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-78606773-T-G is Benign according to our data. Variant chr3-78606773-T-G is described in ClinVar as [Benign]. Clinvar id is 1529664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.544 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0155 (2360/152260) while in subpopulation AFR AF= 0.0209 (867/41554). AF 95% confidence interval is 0.0197. There are 24 homozygotes in gnomad4. There are 1135 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4 linkuse as main transcript	c.4704A>C	p.Ala1568=	synonymous_variant	29/31	ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6 linkuse as main transcript	c.4704A>C	p.Ala1568=	synonymous_variant	29/31	5	NM_002941.4	P3	Q9Y6N7-1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2355

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0209

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0127

AC:

3153

AN:

249230

Hom.:

AF XY:

0.0128

AC XY:

1736

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.0230

Gnomad AMR exome

AF:

0.00985

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00846

Gnomad SAS exome

AF:

0.00712

Gnomad FIN exome

AF:

0.00832

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0143

AC:

20876

AN:

1461672

Hom.:

210

Cov.:

AF XY:

0.0141

AC XY:

10220

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.0356

Gnomad4 SAS exome

AF:

0.00722

Gnomad4 FIN exome

AF:

0.00803

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.0156

GnomAD4 genome

AF:

0.0155

AC:

2360

AN:

152260

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1135

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0209

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0161

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.00688

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0163

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0174

EpiControl

AF:

0.0167

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -

ROBO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

DANN

Benign

0.47

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