3-78627255-T-C

Variant names:

• chr3-78627255-T-C
• rs7625555
• NM_002941.4:c.3875+66A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002941.4(ROBO1):​c.3875+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,525,044 control chromosomes in the GnomAD database, including 213,250 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 0.55 (23496 hom., cov: 33)
  • Exomes 𝑓: 0.52 (189754 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 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.3875+66A>G		intron	N/A	NP_002932.1	Q9Y6N7-1
	ROBO1	NM_133631.4		c.3740+66A>G		intron	N/A	NP_598334.2	Q9Y6N7-5
	ROBO1	NM_001145845.2		c.3575+66A>G		intron	N/A	NP_001139317.1	Q9Y6N7-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.3875+66A>G		intron	N/A	ENSP00000420321.1	Q9Y6N7-1
	ROBO1	ENST00000495273.5	TSL:1	c.3740+66A>G		intron	N/A	ENSP00000420637.1	Q9Y6N7-5
	ROBO1	ENST00000467549.5	TSL:1	c.3575+66A>G		intron	N/A	ENSP00000417992.1	Q9Y6N7-6

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83602 AN: 151992 Hom.: 23459 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.523 AC: 718571 AN: 1372936 Hom.: 189754 AF XY: 0.523 AC XY: 353242 AN XY: 675468

African (AFR) AF: 0.650 AC: 20591 AN: 31696

American (AMR) AF: 0.492 AC: 17577 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 11460 AN: 22770

East Asian (EAS) AF: 0.738 AC: 27988 AN: 37914

South Asian (SAS) AF: 0.527 AC: 39514 AN: 74928

European-Finnish (FIN) AF: 0.511 AC: 25667 AN: 50230

Middle Eastern (MID) AF: 0.516 AC: 2814 AN: 5456

European-Non Finnish (NFE) AF: 0.513 AC: 542682 AN: 1057372

Other (OTH) AF: 0.532 AC: 30278 AN: 56868

GnomAD4 genome AF: 0.550 AC: 83700 AN: 152108 Hom.: 23496 Cov.: 33 AF XY: 0.548 AC XY: 40743 AN XY: 74364

African (AFR) AF: 0.639 AC: 26542 AN: 41508

American (AMR) AF: 0.492 AC: 7522 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3468

East Asian (EAS) AF: 0.703 AC: 3638 AN: 5172

South Asian (SAS) AF: 0.516 AC: 2486 AN: 4818

European-Finnish (FIN) AF: 0.514 AC: 5440 AN: 10588

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34675 AN: 67954

Other (OTH) AF: 0.530 AC: 1117 AN: 2108

Alfa AF: 0.520 Hom.: 31454

Bravo AF: 0.557

Asia WGS AF: 0.617 AC: 2142 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.32
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7625555; hg19: chr3-78676405; COSMIC: COSV71399386; COSMIC: COSV71399386;