chr3-76083413-C-T

Variant names:

• chr3-76083413-C-T
• rs1489100
• NM_001378191.1:c.109+145811C>T

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+145811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,832 control chromosomes in the GnomAD database, including 25,900 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 0.58 (25900 hom., cov: 32)
• Consequence: ROBO2 NM_001378191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.633 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+145811C>T		intron	N/A	NP_001365120.1
	ROBO2	NM_001378190.1		c.109+145811C>T		intron	N/A	NP_001365119.1
	ROBO2	NM_001378195.1		c.109+145811C>T		intron	N/A	NP_001365124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.109+145811C>T		intron	N/A	ENSP00000512767.1
	ROBO2	ENST00000696629.1		c.109+145811C>T		intron	N/A	ENSP00000512766.1
	ROBO2	ENST00000471893.2	TSL:4	c.109+145811C>T		intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88277 AN: 151712 Hom.: 25898 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.582 AC: 88320 AN: 151832 Hom.: 25900 Cov.: 32 AF XY: 0.584 AC XY: 43343 AN XY: 74186

African (AFR) AF: 0.601 AC: 24889 AN: 41434

American (AMR) AF: 0.549 AC: 8362 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2304 AN: 3464

East Asian (EAS) AF: 0.390 AC: 2009 AN: 5154

South Asian (SAS) AF: 0.652 AC: 3141 AN: 4820

European-Finnish (FIN) AF: 0.643 AC: 6762 AN: 10522

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38820 AN: 67890

Other (OTH) AF: 0.607 AC: 1280 AN: 2110

Alfa AF: 0.582 Hom.: 4579

Bravo AF: 0.569

Asia WGS AF: 0.568 AC: 1972 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.61
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1489100; hg19: chr3-76132564;