rs3907672

Variant names:

• chr3-76410695-T-C
• rs3907672
• NM_001394212.1:c.130+99278T>C

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+99278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,136 control chromosomes in the GnomAD database, including 3,112 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 0.19 (3112 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+99278T>C		intron_variant	Intron 1 of 27		NP_001381141.1
ROBO2	NM_001378191.1	c.109+473093T>C		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378192.1	c.130+99278T>C		intron_variant	Intron 1 of 27		NP_001365121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.109+473093T>C		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+473093T>C		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+473093T>C		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28364 AN: 152018 Hom.: 3116 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.187 AC: 28375 AN: 152136 Hom.: 3112 Cov.: 32 AF XY: 0.182 AC XY: 13526 AN XY: 74382

African (AFR) AF: 0.301 AC: 12483 AN: 41512

American (AMR) AF: 0.139 AC: 2124 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3464

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5178

South Asian (SAS) AF: 0.0859 AC: 414 AN: 4820

European-Finnish (FIN) AF: 0.126 AC: 1337 AN: 10600

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10908 AN: 67960

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.171 Hom.: 449

Bravo AF: 0.191

Asia WGS AF: 0.0710 AC: 248 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.73
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs3907672; hg19: chr3-76459846;