3-79018815-C-T

Variant names:

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

Variant summary

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

The NM_133631.4(ROBO1):​c.-354G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 1,026,954 control chromosomes in the GnomAD database, including 499,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.97 (71433 hom., cov: 33)
  • Exomes 𝑓: 0.99 (427749 hom.)
• Consequence: ROBO1 NM_133631.4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133631.4. 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.173-79888G>A		intron	N/A	NP_002932.1	Q9Y6N7-1
	ROBO1	NM_133631.4		c.-354G>A		5_prime_UTR	Exon 1 of 29	NP_598334.2	Q9Y6N7-5
	ROBO1	NM_001145845.2		c.-354G>A		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>A		5_prime_UTR	Exon 1 of 29	ENSP00000420637.1	Q9Y6N7-5
	ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.173-79888G>A		intron	N/A	ENSP00000420321.1	Q9Y6N7-1
	ROBO1	ENST00000436010.6	TSL:5	c.-594G>A		5_prime_UTR	Exon 1 of 29	ENSP00000406043.3	A0A0A0MSX4

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147307 AN: 152146 Hom.: 71409 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.966

GnomAD4 exome AF: 0.989 AC: 864956 AN: 874690 Hom.: 427749 Cov.: 58 AF XY: 0.989 AC XY: 402111 AN XY: 406578

African (AFR) AF: 0.911 AC: 16522 AN: 18134

American (AMR) AF: 0.989 AC: 4405 AN: 4452

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 6431 AN: 6496

East Asian (EAS) AF: 1.00 AC: 7268 AN: 7268

South Asian (SAS) AF: 0.977 AC: 19319 AN: 19782

European-Finnish (FIN) AF: 0.999 AC: 1444 AN: 1446

Middle Eastern (MID) AF: 0.965 AC: 1719 AN: 1782

European-Non Finnish (NFE) AF: 0.991 AC: 778828 AN: 785872

Other (OTH) AF: 0.985 AC: 29020 AN: 29458

GnomAD4 genome AF: 0.968 AC: 147378 AN: 152264 Hom.: 71433 Cov.: 33 AF XY: 0.968 AC XY: 72101 AN XY: 74462

African (AFR) AF: 0.913 AC: 37943 AN: 41540

American (AMR) AF: 0.974 AC: 14901 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3436 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5138 AN: 5138

South Asian (SAS) AF: 0.979 AC: 4723 AN: 4822

European-Finnish (FIN) AF: 0.995 AC: 10578 AN: 10630

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67421 AN: 68034

Other (OTH) AF: 0.963 AC: 2037 AN: 2116

Alfa AF: 0.975 Hom.: 21861

Bravo AF: 0.965

Asia WGS AF: 0.970 AC: 3374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		1.5
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=290/10	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: rs1550930; hg19: chr3-79067965;