3-78649238-T-C

Variant names:

• chr3-78649238-T-C
• rs1032966
• NM_002941.4:c.2813-1583A>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.2813-1583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,064 control chromosomes in the GnomAD database, including 59,370 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 0.88 (59370 hom., cov: 31)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.2813-1583A>G		intron_variant	Intron 19 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.2813-1583A>G		intron_variant	Intron 19 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133661 AN: 151946 Hom.: 59336 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.880 AC: 133751 AN: 152064 Hom.: 59370 Cov.: 31 AF XY: 0.882 AC XY: 65533 AN XY: 74340

African (AFR) AF: 0.748 AC: 30994 AN: 41440

American (AMR) AF: 0.928 AC: 14158 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3216 AN: 3472

East Asian (EAS) AF: 0.918 AC: 4748 AN: 5172

South Asian (SAS) AF: 0.899 AC: 4337 AN: 4822

European-Finnish (FIN) AF: 0.955 AC: 10126 AN: 10604

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63206 AN: 67984

Other (OTH) AF: 0.878 AC: 1857 AN: 2114

Alfa AF: 0.918 Hom.: 32356

Bravo AF: 0.873

Asia WGS AF: 0.894 AC: 3108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		0.40
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: rs1032966; hg19: chr3-78698388;