rs4513416

chr3-79441653-C-T

Variant summary

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

The NM_002941.4(ROBO1):c.88+148171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,860 control chromosomes in the GnomAD database, including 10,349 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 0.35 (10349 hom., cov: 32)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.88+148171G>A		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6	c.88+148171G>A		intron_variant		5	NM_002941.4	P3
	ENST00000660849.1	n.449+12918C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53424 AN: 151742 Hom.: 10342 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.352 AC: 53447 AN: 151860 Hom.: 10349 Cov.: 32 AF XY: 0.356 AC XY: 26444 AN XY: 74228

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.372

Alfa AF: 0.383 Hom.: 2364

Bravo AF: 0.353

Asia WGS AF: 0.428 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	16
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4513416; hg19: chr3-79490803;