chr3-78617615-T-C

Variant names:

• chr3-78617615-T-C
• rs9839790
• NM_002941.4:c.4282+20A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002941.4(ROBO1):​c.4282+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,569,684 control chromosomes in the GnomAD database, including 333,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28119 hom., cov: 32)
  • Exomes 𝑓: 0.65 (305003 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0260
• 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-78617615-T-C is Benign according to our data. Variant chr3-78617615-T-C is described in ClinVar as Benign. ClinVar VariationId is 1241025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.4282+20A>G		intron_variant	Intron 27 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.4282+20A>G		intron_variant	Intron 27 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91382 AN: 151822 Hom.: 28115 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.644

GnomAD2 exomes AF: 0.623 AC: 134874 AN: 216406 AF XY: 0.627

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.614

Gnomad ASJ exome AF: 0.692

Gnomad EAS exome AF: 0.533

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.656

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.654 AC: 927098 AN: 1417746 Hom.: 305003 Cov.: 38 AF XY: 0.653 AC XY: 457453 AN XY: 700548

African (AFR) AF: 0.464 AC: 14908 AN: 32128

American (AMR) AF: 0.618 AC: 24003 AN: 38826

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 15906 AN: 22958

East Asian (EAS) AF: 0.577 AC: 22692 AN: 39298

South Asian (SAS) AF: 0.601 AC: 47630 AN: 79202

European-Finnish (FIN) AF: 0.661 AC: 34314 AN: 51942

Middle Eastern (MID) AF: 0.694 AC: 3784 AN: 5450

European-Non Finnish (NFE) AF: 0.666 AC: 726248 AN: 1089686

Other (OTH) AF: 0.646 AC: 37613 AN: 58256

GnomAD4 genome AF: 0.602 AC: 91418 AN: 151938 Hom.: 28119 Cov.: 32 AF XY: 0.605 AC XY: 44920 AN XY: 74240

African (AFR) AF: 0.465 AC: 19269 AN: 41404

American (AMR) AF: 0.644 AC: 9838 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2380 AN: 3472

East Asian (EAS) AF: 0.557 AC: 2860 AN: 5132

South Asian (SAS) AF: 0.585 AC: 2819 AN: 4822

European-Finnish (FIN) AF: 0.679 AC: 7174 AN: 10558

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44867 AN: 67974

Other (OTH) AF: 0.643 AC: 1352 AN: 2104

Alfa AF: 0.642 Hom.: 126893

Bravo AF: 0.592

Asia WGS AF: 0.551 AC: 1918 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.50
PhyloP100		0.026
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9839790; hg19: chr3-78666765; COSMIC: COSV71397792;