rs4264688

Variant names:

• chr3-79497198-C-T
• rs4264688
• NM_002941.4:c.88+92626G>A

Variant summary

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

The NM_002941.4(ROBO1):​c.88+92626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,032 control chromosomes in the GnomAD database, including 7,485 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 0.31 (7485 hom., cov: 32)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.88+92626G>A		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+92626G>A		intron_variant	Intron 2 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46951 AN: 151912 Hom.: 7478 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.309 AC: 46968 AN: 152032 Hom.: 7485 Cov.: 32 AF XY: 0.310 AC XY: 23049 AN XY: 74324

African (AFR) AF: 0.249 AC: 10330 AN: 41490

American (AMR) AF: 0.240 AC: 3672 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1798 AN: 5156

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4828

European-Finnish (FIN) AF: 0.384 AC: 4052 AN: 10554

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23852 AN: 67936

Other (OTH) AF: 0.293 AC: 619 AN: 2110

Alfa AF: 0.336 Hom.: 4495

Bravo AF: 0.296

Asia WGS AF: 0.311 AC: 1079 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.66
PhyloP100		-0.92
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: rs4264688; hg19: chr3-79546348;