rs9309833

Variant names:

• chr3-79762569-A-G
• rs9309833
• NM_002941.4:c.-51+5183T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-79762569-A-G
• chr3-79762569-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002941.4(ROBO1):​c.-51+5183T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,000 control chromosomes in the GnomAD database, including 4,185 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 0.23 (4185 hom., cov: 31)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.-51+5183T>C		intron_variant	Intron 1 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.-51+5183T>C		intron_variant	Intron 1 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34164 AN: 150880 Hom.: 4181 Cov.: 31

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.226 AC: 34198 AN: 151000 Hom.: 4185 Cov.: 31 AF XY: 0.229 AC XY: 16852 AN XY: 73690

African (AFR) AF: 0.314 AC: 12890 AN: 41002

American (AMR) AF: 0.214 AC: 3244 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3464

East Asian (EAS) AF: 0.319 AC: 1632 AN: 5116

South Asian (SAS) AF: 0.260 AC: 1248 AN: 4804

European-Finnish (FIN) AF: 0.200 AC: 2074 AN: 10358

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12187 AN: 67836

Other (OTH) AF: 0.207 AC: 432 AN: 2086

Alfa AF: 0.0967 Hom.: 128

Bravo AF: 0.232

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.9
DANN	Benign	0.28
PhyloP100		3.5
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: rs9309833; hg19: chr3-79811719;