rs967454

chr3-78688812-G-Achr3-78688812-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002941.4(ROBO1):c.1046-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,570,346 control chromosomes in the GnomAD database, including 173,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (13055 hom., cov: 32)
  • Exomes 𝑓: 0.47 (160063 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.1046-40C>T		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6	c.1046-40C>T		intron_variant		5	NM_002941.4	P3

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56836 AN: 151874 Hom.: 13069 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.412

GnomAD3 exomes AF: 0.442 AC: 88730 AN: 200694 Hom.: 20768 AF XY: 0.447 AC XY: 48116 AN XY: 107526

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.466

Gnomad FIN exome AF: 0.474

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.468 AC: 663863 AN: 1418354 Hom.: 160063 Cov.: 26 AF XY: 0.470 AC XY: 330349 AN XY: 702638

Gnomad4 AFR exome AF: 0.0929

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.487

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.374 AC: 56806 AN: 151992 Hom.: 13055 Cov.: 32 AF XY: 0.378 AC XY: 28038 AN XY: 74270

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.408

Alfa AF: 0.443 Hom.: 3435

Bravo AF: 0.356

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.75
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs967454; hg19: chr3-78737962; COSMIC: COSV71394114; COSMIC: COSV71394114;