ENST00000495273.5:c.-354G>C

Variant names:

• chr3-79018815-C-G
• rs1550930
• ENST00000495273.5:c.-354G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000495273.5(ROBO1):​c.-354G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROBO1 ENST00000495273.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000495273.5. 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.173-79888G>C		intron	N/A	NP_002932.1	Q9Y6N7-1
	ROBO1	NM_133631.4		c.-354G>C		5_prime_UTR	Exon 1 of 29	NP_598334.2	Q9Y6N7-5
	ROBO1	NM_001145845.2		c.-354G>C		5_prime_UTR	Exon 1 of 29	NP_001139317.1	Q9Y6N7-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	ENST00000495273.5	TSL:1	c.-354G>C		5_prime_UTR	Exon 1 of 29	ENSP00000420637.1	Q9Y6N7-5
	ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.173-79888G>C		intron	N/A	ENSP00000420321.1	Q9Y6N7-1
	ROBO1	ENST00000436010.6	TSL:5	c.-594G>C		5_prime_UTR	Exon 1 of 29	ENSP00000406043.3	A0A0A0MSX4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 874700 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 406586

African (AFR) AF: 0.00 AC: 0 AN: 18136

American (AMR) AF: 0.00 AC: 0 AN: 4454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6496

East Asian (EAS) AF: 0.00 AC: 0 AN: 7268

South Asian (SAS) AF: 0.00 AC: 0 AN: 19782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1782

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 785878

Other (OTH) AF: 0.00 AC: 0 AN: 29458

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		1.5
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1550930; hg19: chr3-79067965;