3-78608848-C-T

Variant names:

• chr3-78608848-C-T
• rs723765
• NM_002941.4:c.4436-1807G>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.4436-1807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,774 control chromosomes in the GnomAD database, including 23,535 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 0.55 (23535 hom., cov: 31)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• Publications: 16 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 (EAS) allele frequency at 95% confidence interval = 0.778 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.4436-1807G>A		intron	N/A	NP_002932.1
	ROBO1	NM_133631.4		c.4301-1807G>A		intron	N/A	NP_598334.2
	ROBO1	NM_001145845.2		c.4136-1807G>A		intron	N/A	NP_001139317.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.4436-1807G>A		intron	N/A	ENSP00000420321.1
	ROBO1	ENST00000495273.5	TSL:1	c.4301-1807G>A		intron	N/A	ENSP00000420637.1
	ROBO1	ENST00000467549.5	TSL:1	c.4136-1807G>A		intron	N/A	ENSP00000417992.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82919 AN: 151654 Hom.: 23489 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.547 AC: 83016 AN: 151774 Hom.: 23535 Cov.: 31 AF XY: 0.554 AC XY: 41077 AN XY: 74156

African (AFR) AF: 0.662 AC: 27407 AN: 41380

American (AMR) AF: 0.515 AC: 7851 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1706 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4110 AN: 5148

South Asian (SAS) AF: 0.652 AC: 3133 AN: 4804

European-Finnish (FIN) AF: 0.592 AC: 6243 AN: 10538

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30834 AN: 67888

Other (OTH) AF: 0.516 AC: 1086 AN: 2106

Alfa AF: 0.487 Hom.: 41771

Bravo AF: 0.546

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.76
DANN	Benign	0.45
PhyloP100		-0.051
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs723765; hg19: chr3-78657998;