Variant 3-78614806-G-A 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.4283-6C>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003322

Clinical Significance

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

Conservation

PhyloP100: -0.360

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
ROBO1	NM_002941.4 linkuse as main transcript	c.4283-6C>T		splice_region_variant, splice_polypyrimidine_tract_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.4283-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_002941.4	P3	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

GnomAD3 exomes

AF:

0.454

AC:

80681

AN:

177654

Hom.:

17536

AF XY:

0.453

AC XY:

43496

AN XY:

96102

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 SAS exome

AF:

0.458

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

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.373

AC:

54888

AN:

147144

Hom.:

11037

Cov.:

AF XY:

0.380

AC XY:

27149

AN XY:

71536

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.325

Gnomad4 SAS

AF:

0.434

Gnomad4 FIN

AF:

0.487

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.409

Hom.:

25242

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

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

DANN

Benign

0.44

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

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