3-79501223-A-G

Variant names:

• chr3-79501223-A-G
• rs6548621
• NM_002941.4:c.88+88601T>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+88601T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,038 control chromosomes in the GnomAD database, including 33,657 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 0.66 (33657 hom., cov: 32)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.826 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	NM_002941.4	MANE Select	c.88+88601T>C		intron	N/A	NP_002932.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.88+88601T>C		intron	N/A	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99597 AN: 151918 Hom.: 33619 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.656 AC: 99694 AN: 152038 Hom.: 33657 Cov.: 32 AF XY: 0.652 AC XY: 48462 AN XY: 74318

African (AFR) AF: 0.833 AC: 34565 AN: 41472

American (AMR) AF: 0.603 AC: 9203 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2793 AN: 5160

South Asian (SAS) AF: 0.606 AC: 2917 AN: 4812

European-Finnish (FIN) AF: 0.602 AC: 6359 AN: 10570

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40069 AN: 67968

Other (OTH) AF: 0.633 AC: 1336 AN: 2112

Alfa AF: 0.607 Hom.: 48462

Bravo AF: 0.664

Asia WGS AF: 0.578 AC: 2011 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	5.4
DANN	Benign	0.77
PhyloP100		1.3
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: rs6548621; hg19: chr3-79550373;