3-79018815-C-T

Position:

• chr3-79018815-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000495273.5(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.97 (71433 hom., cov: 33)
  • Exomes 𝑓: 0.99 (427749 hom.)
• Consequence: ROBO1 ENST00000495273.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.173-79888G>A		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000495273.5	c.-354G>A		5_prime_UTR_variant	1/29	1		A1
ROBO1	ENST00000464233.6	c.173-79888G>A		intron_variant		5	NM_002941.4	P3
ROBO1	ENST00000436010.6	c.-594G>A		5_prime_UTR_variant	1/29	5
ROBO1	ENST00000618846.4	c.-594G>A		5_prime_UTR_variant	1/29	5

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

Gnomad4 AFR exome AF: 0.911

Gnomad4 AMR exome AF: 0.989

Gnomad4 ASJ exome AF: 0.990

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.977

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 0.991

Gnomad4 OTH exome AF: 0.985

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

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.990

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.963

Alfa AF: 0.970 Hom.: 11699

Bravo AF: 0.965

Asia WGS AF: 0.970 AC: 3374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.90
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

Publications

LitVar

Other links and lift over

dbSNP: rs1550930; hg19: chr3-79067965;