rs1387665

chr3-79380661-G-Achr3-79380661-G-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+209163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,722 control chromosomes in the GnomAD database, including 19,454 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 0.50 (19454 hom., cov: 30)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.88+209163C>T		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6	c.88+209163C>T		intron_variant		5	NM_002941.4	P3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76541 AN: 151604 Hom.: 19452 Cov.: 30

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.505 AC: 76571 AN: 151722 Hom.: 19454 Cov.: 30 AF XY: 0.503 AC XY: 37288 AN XY: 74112

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.496

Alfa AF: 0.491 Hom.: 23958

Bravo AF: 0.497

Asia WGS AF: 0.432 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1387665; hg19: chr3-79429811;