NM_002941.4:c.88+57724C>T

Variant names:

• chr3-79532100-G-A
• rs4279056
• NM_002941.4:c.88+57724C>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.88+57724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,904 control chromosomes in the GnomAD database, including 24,979 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 0.57 (24979 hom., cov: 31)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.591 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+57724C>T		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+57724C>T		intron	N/A	ENSP00000420321.1	Q9Y6N7-1
	ROBO1	ENST00000492990.1	TSL:3	n.*58+914C>T		intron	N/A	ENSP00000419915.1	F8WEV8

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86819 AN: 151786 Hom.: 24954 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.572 AC: 86894 AN: 151904 Hom.: 24979 Cov.: 31 AF XY: 0.570 AC XY: 42324 AN XY: 74214

African (AFR) AF: 0.575 AC: 23820 AN: 41414

American (AMR) AF: 0.469 AC: 7155 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2603 AN: 5146

South Asian (SAS) AF: 0.486 AC: 2335 AN: 4800

European-Finnish (FIN) AF: 0.629 AC: 6646 AN: 10564

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40477 AN: 67942

Other (OTH) AF: 0.577 AC: 1218 AN: 2112

Alfa AF: 0.569 Hom.: 3081

Bravo AF: 0.559

Asia WGS AF: 0.486 AC: 1690 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	2.1
DANN	Benign	0.49
PhyloP100		-0.14
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: rs4279056; hg19: chr3-79581250;