chr3-78859021-T-C

Variant names:

• chr3-78859021-T-C
• rs1383407
• NM_002941.4:c.499+79580A>G

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_002941.4(ROBO1):​c.499+79580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,922 control chromosomes in the GnomAD database, including 10,387 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 0.33 (10387 hom., cov: 31)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 10 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 (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.499+79580A>G		intron_variant	Intron 4 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.499+79580A>G		intron_variant	Intron 4 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50752 AN: 151802 Hom.: 10394 Cov.: 31

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.334 AC: 50738 AN: 151922 Hom.: 10387 Cov.: 31 AF XY: 0.340 AC XY: 25262 AN XY: 74226

African (AFR) AF: 0.0844 AC: 3501 AN: 41488

American (AMR) AF: 0.422 AC: 6446 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1599 AN: 3466

East Asian (EAS) AF: 0.407 AC: 2089 AN: 5134

South Asian (SAS) AF: 0.528 AC: 2540 AN: 4808

European-Finnish (FIN) AF: 0.417 AC: 4389 AN: 10528

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28800 AN: 67922

Other (OTH) AF: 0.346 AC: 730 AN: 2110

Alfa AF: 0.403 Hom.: 20194

Bravo AF: 0.320

Asia WGS AF: 0.409 AC: 1424 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	5.9
DANN	Benign	0.60
PhyloP100		0.55
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: rs1383407; hg19: chr3-78908171;