rs7614084

chr3-78627272-G-A

Variant summary

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

The NM_002941.4(ROBO1):c.3875+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,576,350 control chromosomes in the GnomAD database, including 127,485 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 (10984 hom., cov: 33)
  • Exomes 𝑓: 0.40 (116501 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

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 (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.3875+49C>T		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6	c.3875+49C>T		intron_variant		5	NM_002941.4	P3

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56627 AN: 151936 Hom.: 10987 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.408

GnomAD3 exomes AF: 0.394 AC: 84184 AN: 213820 Hom.: 16756 AF XY: 0.391 AC XY: 45047 AN XY: 115064

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.261

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.402 AC: 572014 AN: 1424296 Hom.: 116501 Cov.: 28 AF XY: 0.401 AC XY: 282608 AN XY: 704410

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.372 AC: 56638 AN: 152054 Hom.: 10984 Cov.: 33 AF XY: 0.375 AC XY: 27885 AN XY: 74306

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.405

Alfa AF: 0.407 Hom.: 21191

Bravo AF: 0.370

Asia WGS AF: 0.317 AC: 1105 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	1.7
Dann	Benign	0.66

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: rs7614084; hg19: chr3-78676422; COSMIC: COSV71394443; COSMIC: COSV71394443;