chr3-77482775-G-A

Variant names:

• chr3-77482775-G-A
• rs1470569
• NM_001395656.1:c.667+1556G>A

Variant summary

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

The NM_001395656.1(ROBO2):​c.667+1556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,624 control chromosomes in the GnomAD database, including 21,020 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 0.52 (21020 hom., cov: 30)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395656.1. 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_001395656.1	MANE Select	c.667+1556G>A		intron	N/A	NP_001382585.1
	ROBO2	NM_001394212.1		c.736+1556G>A		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.715+1556G>A		intron	N/A	NP_001365120.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696593.1	MANE Select	c.667+1556G>A		intron	N/A	ENSP00000512738.1
	ROBO2	ENST00000461745.5	TSL:1	c.667+1556G>A		intron	N/A	ENSP00000417164.1
	ROBO2	ENST00000473767.5	TSL:1	n.667+1556G>A		intron	N/A	ENSP00000418117.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79150 AN: 151504 Hom.: 21001 Cov.: 30

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.522 AC: 79202 AN: 151624 Hom.: 21020 Cov.: 30 AF XY: 0.525 AC XY: 38885 AN XY: 74064

African (AFR) AF: 0.427 AC: 17652 AN: 41300

American (AMR) AF: 0.630 AC: 9593 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2045 AN: 3466

East Asian (EAS) AF: 0.605 AC: 3106 AN: 5136

South Asian (SAS) AF: 0.569 AC: 2726 AN: 4794

European-Finnish (FIN) AF: 0.563 AC: 5911 AN: 10508

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36461 AN: 67880

Other (OTH) AF: 0.558 AC: 1175 AN: 2104

Alfa AF: 0.536 Hom.: 62050

Bravo AF: 0.526

Asia WGS AF: 0.611 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.50
PhyloP100		-0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1470569; hg19: chr3-77531926;