3-76212669-T-C

Variant names:

• chr3-76212669-T-C
• rs1516459
• NM_001378191.1:c.109+275067T>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+275067T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,164 control chromosomes in the GnomAD database, including 67,790 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 0.94 (67790 hom., cov: 32)
• Consequence: ROBO2 NM_001378191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 5 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, 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	NM_001378191.1		c.109+275067T>C		intron	N/A	NP_001365120.1
	ROBO2	NM_001378190.1		c.109+275067T>C		intron	N/A	NP_001365119.1
	ROBO2	NM_001378195.1		c.109+275067T>C		intron	N/A	NP_001365124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.109+275067T>C		intron	N/A	ENSP00000512767.1
	ROBO2	ENST00000696629.1		c.109+275067T>C		intron	N/A	ENSP00000512766.1
	ROBO2	ENST00000471893.2	TSL:4	c.109+275067T>C		intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143370 AN: 152048 Hom.: 67748 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.943

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

GnomAD4 genome AF: 0.943 AC: 143468 AN: 152164 Hom.: 67790 Cov.: 32 AF XY: 0.944 AC XY: 70226 AN XY: 74386

African (AFR) AF: 0.868 AC: 36042 AN: 41520

American (AMR) AF: 0.944 AC: 14413 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3356 AN: 3470

East Asian (EAS) AF: 0.986 AC: 5084 AN: 5158

South Asian (SAS) AF: 0.960 AC: 4633 AN: 4828

European-Finnish (FIN) AF: 0.988 AC: 10502 AN: 10626

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.975 AC: 66260 AN: 67976

Other (OTH) AF: 0.943 AC: 1988 AN: 2108

Alfa AF: 0.960 Hom.: 106398

Bravo AF: 0.934

Asia WGS AF: 0.951 AC: 3305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.62
DANN	Benign	0.47
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs1516459; hg19: chr3-76261820;