NM_001394212.1:c.130+48243C>T

Variant names:

• chr3-76359660-C-T
• rs3860546
• NM_001394212.1:c.130+48243C>T

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+48243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,820 control chromosomes in the GnomAD database, including 7,780 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 0.24 (7780 hom., cov: 31)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+48243C>T		intron_variant	Intron 1 of 27		NP_001381141.1
ROBO2	NM_001378191.1	c.109+422058C>T		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378192.1	c.130+48243C>T		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+422058C>T		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+422058C>T		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+422058C>T		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37082 AN: 151702 Hom.: 7756 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.245 AC: 37157 AN: 151820 Hom.: 7780 Cov.: 31 AF XY: 0.240 AC XY: 17777 AN XY: 74194

African (AFR) AF: 0.570 AC: 23582 AN: 41378

American (AMR) AF: 0.214 AC: 3249 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3466

East Asian (EAS) AF: 0.0430 AC: 221 AN: 5138

South Asian (SAS) AF: 0.0985 AC: 474 AN: 4812

European-Finnish (FIN) AF: 0.0843 AC: 892 AN: 10580

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7690 AN: 67922

Other (OTH) AF: 0.246 AC: 519 AN: 2108

Alfa AF: 0.188 Hom.: 643

Bravo AF: 0.270

Asia WGS AF: 0.127 AC: 443 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.0
DANN	Benign	0.15
PhyloP100		0.94

Splicing

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

Other links and lift over

dbSNP: rs3860546; hg19: chr3-76408811;