rs2255164

chr3-78668358-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.1631-56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,597,854 control chromosomes in the GnomAD database, including 194,176 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 0.46 (16749 hom., cov: 32)
  • Exomes 𝑓: 0.49 (177427 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.1631-56C>T		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6	c.1631-56C>T		intron_variant		5	NM_002941.4	P3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70193 AN: 151842 Hom.: 16759 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.492 AC: 711080 AN: 1445894 Hom.: 177427 Cov.: 28 AF XY: 0.492 AC XY: 353766 AN XY: 718570

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.484

GnomAD4 genome AF: 0.462 AC: 70198 AN: 151960 Hom.: 16749 Cov.: 32 AF XY: 0.463 AC XY: 34350 AN XY: 74270

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.480

Alfa AF: 0.504 Hom.: 18303

Bravo AF: 0.455

Asia WGS AF: 0.314 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.4
Dann	Benign	0.39

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: rs2255164; hg19: chr3-78717508; COSMIC: COSV71394474;