rs1489092

Positions:

• chr3-76072355-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO2	NM_001128929.3	c.109+134753T>C		intron_variant			NP_001122401.1
ROBO2	NM_001378190.1	c.109+134753T>C		intron_variant			NP_001365119.1
ROBO2	NM_001378191.1	c.109+134753T>C		intron_variant			NP_001365120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000471893.2	c.109+134753T>C		intron_variant		4		ENSP00000418190
ROBO2	ENST00000487694.7	c.109+134753T>C		intron_variant		5		ENSP00000417335
ROBO2	ENST00000602589.5	c.109+134753T>C		intron_variant		5		ENSP00000473268

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

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.652

Alfa AF: 0.592 Hom.: 22534

Bravo AF: 0.623

Asia WGS AF: 0.582 AC: 2011 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1489092; hg19: chr3-76121506;