NM_002941.4:c.-51+56128C>T

Variant names:

• chr3-79711624-G-A
• rs9309828
• NM_002941.4:c.-51+56128C>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+56128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,834 control chromosomes in the GnomAD database, including 7,154 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 0.29 (7154 hom., cov: 32)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• 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: 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.-51+56128C>T		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+56128C>T		intron_variant	Intron 1 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43456 AN: 151716 Hom.: 7144 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.287 AC: 43512 AN: 151834 Hom.: 7154 Cov.: 32 AF XY: 0.283 AC XY: 21030 AN XY: 74214

African (AFR) AF: 0.455 AC: 18802 AN: 41358

American (AMR) AF: 0.195 AC: 2974 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3472

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5170

South Asian (SAS) AF: 0.198 AC: 952 AN: 4812

European-Finnish (FIN) AF: 0.268 AC: 2824 AN: 10534

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16373 AN: 67946

Other (OTH) AF: 0.259 AC: 547 AN: 2108

Alfa AF: 0.248 Hom.: 2314

Bravo AF: 0.287

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.49
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: rs9309828; hg19: chr3-79760774;