3-79554914-C-T

Variant names:

• chr3-79554914-C-T
• rs7617400
• NM_002941.4:c.88+34910G>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+34910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,836 control chromosomes in the GnomAD database, including 4,910 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 0.24 (4910 hom., cov: 32)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 5 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• pituitary hormone deficiency, combined or isolated, 8

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen
• nystagmus, congenital, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	NM_002941.4	MANE Select	c.88+34910G>A		intron	N/A	NP_002932.1	Q9Y6N7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.88+34910G>A		intron	N/A	ENSP00000420321.1	Q9Y6N7-1
	ROBO1	ENST00000492990.1	TSL:3	n.89-21805G>A		intron	N/A	ENSP00000419915.1	F8WEV8

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36257 AN: 151718 Hom.: 4905 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.239 AC: 36301 AN: 151836 Hom.: 4910 Cov.: 32 AF XY: 0.233 AC XY: 17331 AN XY: 74236

African (AFR) AF: 0.361 AC: 14960 AN: 41414

American (AMR) AF: 0.191 AC: 2910 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3470

East Asian (EAS) AF: 0.158 AC: 814 AN: 5166

South Asian (SAS) AF: 0.202 AC: 973 AN: 4812

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10556

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13247 AN: 67890

Other (OTH) AF: 0.240 AC: 506 AN: 2106

Alfa AF: 0.205 Hom.: 5880

Bravo AF: 0.247

Asia WGS AF: 0.190 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.53
PhyloP100		-2.1
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: rs7617400; hg19: chr3-79604064;