rs1383407

chr3-78859021-T-C

Variant summary

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

The NM_002941.4(ROBO1):c.499+79580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,922 control chromosomes in the GnomAD database, including 10,387 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 0.33 (10387 hom., cov: 31)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.499+79580A>G		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6	c.499+79580A>G		intron_variant		5	NM_002941.4	P3

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50752 AN: 151802 Hom.: 10394 Cov.: 31

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.334 AC: 50738 AN: 151922 Hom.: 10387 Cov.: 31 AF XY: 0.340 AC XY: 25262 AN XY: 74226

Gnomad4 AFR AF: 0.0844

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.346

Alfa AF: 0.417 Hom.: 15253

Bravo AF: 0.320

Asia WGS AF: 0.409 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.9
Dann	Benign	0.60

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: rs1383407; hg19: chr3-78908171;