3-79479910-C-G

Variant names:

• chr3-79479910-C-G
• rs7631357
• NM_002941.4:c.88+109914G>C

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+109914G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,944 control chromosomes in the GnomAD database, including 17,143 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 0.47 (17143 hom., cov: 32)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.88+109914G>C		intron_variant	Intron 2 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.88+109914G>C		intron_variant	Intron 2 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71969 AN: 151826 Hom.: 17137 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.474 AC: 72003 AN: 151944 Hom.: 17143 Cov.: 32 AF XY: 0.473 AC XY: 35137 AN XY: 74280

African (AFR) AF: 0.452 AC: 18716 AN: 41442

American (AMR) AF: 0.418 AC: 6372 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3466

East Asian (EAS) AF: 0.382 AC: 1977 AN: 5172

South Asian (SAS) AF: 0.498 AC: 2404 AN: 4824

European-Finnish (FIN) AF: 0.505 AC: 5327 AN: 10550

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34078 AN: 67918

Other (OTH) AF: 0.478 AC: 1008 AN: 2110

Alfa AF: 0.485 Hom.: 2246

Bravo AF: 0.462

Asia WGS AF: 0.425 AC: 1476 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.55
PhyloP100		0.066
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: rs7631357; hg19: chr3-79529060;