rs13076006

Variant names:

• chr3-79403486-A-C
• rs13076006
• NM_002941.4:c.88+186338T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-79403486-A-C
• chr3-79403486-A-G
• chr3-79403486-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002941.4(ROBO1):​c.88+186338T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,742 control chromosomes in the GnomAD database, including 10,835 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 (10835 hom., cov: 32)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• Publications: 2 publications found

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]

ROBO1 Gene-Disease associations (from GenCC):

• neurooculorenal syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary hormone deficiency, combined or isolated, 8

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.88+186338T>G		intron_variant	Intron 2 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.88+186338T>G		intron_variant	Intron 2 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55594 AN: 151624 Hom.: 10826 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.367 AC: 55629 AN: 151742 Hom.: 10835 Cov.: 32 AF XY: 0.371 AC XY: 27502 AN XY: 74152

African (AFR) AF: 0.233 AC: 9646 AN: 41478

American (AMR) AF: 0.492 AC: 7487 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1503 AN: 3462

East Asian (EAS) AF: 0.468 AC: 2404 AN: 5138

South Asian (SAS) AF: 0.421 AC: 2031 AN: 4824

European-Finnish (FIN) AF: 0.398 AC: 4193 AN: 10548

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 26999 AN: 67780

Other (OTH) AF: 0.382 AC: 805 AN: 2106

Alfa AF: 0.383 Hom.: 1438

Bravo AF: 0.370

Asia WGS AF: 0.439 AC: 1524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.64
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13076006; hg19: chr3-79452636;