3-76425934-G-C

Position:

• chr3-76425934-G-C

Variant summary

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

The NM_001394212.1(ROBO2):​c.130+114517G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,010 control chromosomes in the GnomAD database, including 34,484 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 0.67 (34484 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO2	NM_001128929.3	c.109+488332G>C		intron_variant
ROBO2	NM_001378190.1	c.109+488332G>C		intron_variant
ROBO2	NM_001378191.1	c.109+488332G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO2	ENST00000471893.2	c.109+488332G>C		intron_variant		4
ROBO2	ENST00000475334.2	c.130+114517G>C		intron_variant		5		A1
ROBO2	ENST00000487694.7	c.109+488332G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101177 AN: 151892 Hom.: 34435 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.666 AC: 101287 AN: 152010 Hom.: 34484 Cov.: 32 AF XY: 0.668 AC XY: 49614 AN XY: 74284

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.648

Alfa AF: 0.468 Hom.: 1164

Bravo AF: 0.676

Asia WGS AF: 0.608 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.072
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9827843; hg19: chr3-76475085;