chr3-76119418-G-A

Variant names:

• chr3-76119418-G-A
• rs4124239
• NM_001378191.1:c.109+181816G>A

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+181816G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 151,920 control chromosomes in the GnomAD database, including 1,241 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 0.087 (1241 hom., cov: 31)
• Consequence: ROBO2 NM_001378191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001378191.1	c.109+181816G>A		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378190.1	c.109+181816G>A		intron_variant	Intron 2 of 28		NP_001365119.1
ROBO2	NM_001378195.1	c.109+181816G>A		intron_variant	Intron 2 of 28		NP_001365124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.109+181816G>A		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+181816G>A		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+181816G>A		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13128 AN: 151802 Hom.: 1231 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.00768

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00724

Gnomad OTH AF: 0.0884

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

GnomAD4 genome AF: 0.0867 AC: 13174 AN: 151920 Hom.: 1241 Cov.: 31 AF XY: 0.0883 AC XY: 6560 AN XY: 74274

African (AFR) AF: 0.223 AC: 9231 AN: 41440

American (AMR) AF: 0.126 AC: 1922 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3470

East Asian (EAS) AF: 0.155 AC: 798 AN: 5144

South Asian (SAS) AF: 0.0531 AC: 255 AN: 4806

European-Finnish (FIN) AF: 0.00768 AC: 81 AN: 10542

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.00724 AC: 492 AN: 67954

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.0392 Hom.: 1107

Bravo AF: 0.103

Asia WGS AF: 0.128 AC: 442 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs4124239; hg19: chr3-76168569;