NM_001395656.1:c.807-5981T>C

Variant names:

• chr3-77516794-T-C
• rs1470572
• NM_001395656.1:c.807-5981T>C

Variant summary

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

The NM_001395656.1(ROBO2):​c.807-5981T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 151,528 control chromosomes in the GnomAD database, including 48,380 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 0.79 (48380 hom., cov: 33)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 3 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, PanelApp Australia, 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 (AFR) allele frequency at 95% confidence interval = 0.923 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	NM_001395656.1	MANE Select	c.807-5981T>C		intron	N/A	NP_001382585.1	A0A8Q3WLE3
	ROBO2	NM_001394212.1		c.876-5981T>C		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.855-5981T>C		intron	N/A	NP_001365120.1	A0A8Q3SIW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696593.1	MANE Select	c.807-5981T>C		intron	N/A	ENSP00000512738.1	A0A8Q3WLE3
	ROBO2	ENST00000461745.5	TSL:1	c.807-5981T>C		intron	N/A	ENSP00000417164.1	Q9HCK4-1
	ROBO2	ENST00000473767.5	TSL:1	n.807-5981T>C		intron	N/A	ENSP00000418117.1	F8WBR3

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120037 AN: 151410 Hom.: 48320 Cov.: 33

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.793 AC: 120160 AN: 151528 Hom.: 48380 Cov.: 33 AF XY: 0.797 AC XY: 58985 AN XY: 74034

African (AFR) AF: 0.931 AC: 38595 AN: 41456

American (AMR) AF: 0.830 AC: 12554 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2822 AN: 3454

East Asian (EAS) AF: 0.805 AC: 4120 AN: 5116

South Asian (SAS) AF: 0.776 AC: 3744 AN: 4824

European-Finnish (FIN) AF: 0.761 AC: 8059 AN: 10584

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47725 AN: 67652

Other (OTH) AF: 0.815 AC: 1713 AN: 2102

Alfa AF: 0.764 Hom.: 7855

Bravo AF: 0.806

Asia WGS AF: 0.810 AC: 2816 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.67
PhyloP100		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1470572; hg19: chr3-77565945; COSMIC: COSV59916625;