3-76531488-T-A

Variant names:

• chr3-76531488-T-A
• rs1839049
• NM_001394212.1:c.130+220071T>A

Variant summary

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

The NM_001394212.1(ROBO2):​c.130+220071T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 151,754 control chromosomes in the GnomAD database, including 881 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 0.090 (881 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394212.1. 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_001394212.1		c.130+220071T>A		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.110-566526T>A		intron	N/A	NP_001365120.1
	ROBO2	NM_001378192.1		c.130+220071T>A		intron	N/A	NP_001365121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.110-566526T>A		intron	N/A	ENSP00000512767.1
	ROBO2	ENST00000696629.1		c.110-566526T>A		intron	N/A	ENSP00000512766.1
	ROBO2	ENST00000471893.2	TSL:4	c.110-566526T>A		intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13598 AN: 151636 Hom.: 879 Cov.: 32

Gnomad AFR AF: 0.0593

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.0933

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

GnomAD4 genome AF: 0.0897 AC: 13617 AN: 151754 Hom.: 881 Cov.: 32 AF XY: 0.0969 AC XY: 7195 AN XY: 74226

African (AFR) AF: 0.0593 AC: 2459 AN: 41502

American (AMR) AF: 0.189 AC: 2873 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3464

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5170

South Asian (SAS) AF: 0.116 AC: 558 AN: 4792

European-Finnish (FIN) AF: 0.129 AC: 1348 AN: 10474

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0694 AC: 4709 AN: 67822

Other (OTH) AF: 0.0947 AC: 199 AN: 2102

Alfa AF: 0.0768 Hom.: 65

Bravo AF: 0.0936

Asia WGS AF: 0.173 AC: 592 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.67
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs1839049; hg19: chr3-76580639;