rs1489092

Variant names:

• chr3-76072355-T-C
• rs1489092
• NM_001378191.1:c.109+134753T>C

Variant summary

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

The NM_001378191.1(ROBO2):​c.109+134753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,940 control chromosomes in the GnomAD database, including 30,670 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 0.63 (30670 hom., cov: 32)
• Consequence: ROBO2 NM_001378191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 3 publications found

Genes affected

ROBO2 (HGNC:10250): (roundabout guidance receptor 2) The protein encoded by this gene belongs to the ROBO family, part of the immunoglobulin superfamily of proteins that are highly conserved from fly to human. The encoded protein is a transmembrane receptor for the slit homolog 2 protein and functions in axon guidance and cell migration. Mutations in this gene are associated with vesicoureteral reflux, characterized by the backward flow of urine from the bladder into the ureters or the kidney. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ROBO2 Gene-Disease associations (from GenCC):

• vesicoureteral reflux 2

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• familial vesicoureteral reflux

  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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378191.1. 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
	ROBO2	NM_001378191.1		c.109+134753T>C		intron	N/A	NP_001365120.1	A0A8Q3SIW8
	ROBO2	NM_001378190.1		c.109+134753T>C		intron	N/A	NP_001365119.1
	ROBO2	NM_001378195.1		c.109+134753T>C		intron	N/A	NP_001365124.1	A0A8Q3SIU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.109+134753T>C		intron	N/A	ENSP00000512767.1	A0A8Q3SIW8
	ROBO2	ENST00000696629.1		c.109+134753T>C		intron	N/A	ENSP00000512766.1	A0A8Q3SIU0
	ROBO2	ENST00000471893.2	TSL:4	c.109+134753T>C		intron	N/A	ENSP00000418190.2	H7C4U9

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95425 AN: 151822 Hom.: 30653 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.628 AC: 95488 AN: 151940 Hom.: 30670 Cov.: 32 AF XY: 0.629 AC XY: 46721 AN XY: 74264

African (AFR) AF: 0.747 AC: 30973 AN: 41468

American (AMR) AF: 0.572 AC: 8742 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1992 AN: 5152

South Asian (SAS) AF: 0.656 AC: 3164 AN: 4822

European-Finnish (FIN) AF: 0.643 AC: 6744 AN: 10494

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39352 AN: 67946

Other (OTH) AF: 0.652 AC: 1376 AN: 2110

Alfa AF: 0.609 Hom.: 35124

Bravo AF: 0.623

Asia WGS AF: 0.582 AC: 2011 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.048
DANN	Benign	0.40
PhyloP100		-2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1489092; hg19: chr3-76121506;