NM_002941.4:c.-51+32774T>A

Variant names:

• chr3-79734978-A-T
• rs3923526
• NM_002941.4:c.-51+32774T>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.-51+32774T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,140 control chromosomes in the GnomAD database, including 5,539 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 0.25 (5539 hom., cov: 33)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.-51+32774T>A		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+32774T>A		intron_variant	Intron 1 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38099 AN: 152022 Hom.: 5529 Cov.: 33

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.251 AC: 38148 AN: 152140 Hom.: 5539 Cov.: 33 AF XY: 0.251 AC XY: 18636 AN XY: 74390

African (AFR) AF: 0.401 AC: 16612 AN: 41472

American (AMR) AF: 0.225 AC: 3448 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1667 AN: 5170

South Asian (SAS) AF: 0.225 AC: 1087 AN: 4826

European-Finnish (FIN) AF: 0.196 AC: 2079 AN: 10604

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12251 AN: 67990

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.223 Hom.: 541

Bravo AF: 0.262

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.35
PhyloP100		0.42
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: rs3923526; hg19: chr3-79784128;