rs10511040

Positions:

• chr3-76227391-G-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+289789G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,080 control chromosomes in the GnomAD database, including 1,386 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 0.11 (1386 hom., cov: 33)
• Consequence: ROBO2 NM_001378191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO2	NM_001128929.3	c.109+289789G>C		intron_variant			NP_001122401.1
ROBO2	NM_001378190.1	c.109+289789G>C		intron_variant			NP_001365119.1
ROBO2	NM_001378191.1	c.109+289789G>C		intron_variant			NP_001365120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000471893.2	c.109+289789G>C		intron_variant		4		ENSP00000418190
ROBO2	ENST00000487694.7	c.109+289789G>C		intron_variant		5		ENSP00000417335
ROBO2	ENST00000602589.5	c.109+289789G>C		intron_variant		5		ENSP00000473268

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17122 AN: 151962 Hom.: 1381 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.113 AC: 17149 AN: 152080 Hom.: 1386 Cov.: 33 AF XY: 0.115 AC XY: 8525 AN XY: 74346

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0804 Hom.: 108

Bravo AF: 0.131

Asia WGS AF: 0.202 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10511040; hg19: chr3-76276542;