3-77061349-C-G

Variant names:

• chr3-77061349-C-G
• rs4476545
• NM_001395656.1:c.61+20503C>G

Variant summary

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

The NM_001395656.1(ROBO2):​c.61+20503C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,034 control chromosomes in the GnomAD database, including 41,948 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 0.73 (41948 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.61+20503C>G		intron_variant	Intron 1 of 27	ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.61+20503C>G		intron_variant	Intron 1 of 27		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111328 AN: 151916 Hom.: 41942 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.733 AC: 111383 AN: 152034 Hom.: 41948 Cov.: 32 AF XY: 0.731 AC XY: 54335 AN XY: 74300

African (AFR) AF: 0.556 AC: 23040 AN: 41460

American (AMR) AF: 0.721 AC: 11008 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2988 AN: 3468

East Asian (EAS) AF: 0.659 AC: 3388 AN: 5138

South Asian (SAS) AF: 0.767 AC: 3702 AN: 4828

European-Finnish (FIN) AF: 0.770 AC: 8140 AN: 10568

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56442 AN: 67986

Other (OTH) AF: 0.746 AC: 1579 AN: 2116

Alfa AF: 0.769 Hom.: 5689

Bravo AF: 0.727

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4476545; hg19: chr3-77110500;