rs775748

Positions:

• chr3-77547309-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395656.1(ROBO2):​c.1071+847T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,922 control chromosomes in the GnomAD database, including 22,388 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 0.54 (22388 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.1071+847T>A		intron_variant		ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.1071+847T>A		intron_variant			NM_001395656.1	ENSP00000512738	A2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82289 AN: 151806 Hom.: 22390 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.542 AC: 82306 AN: 151922 Hom.: 22388 Cov.: 32 AF XY: 0.543 AC XY: 40331 AN XY: 74246

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.579

Alfa AF: 0.532 Hom.: 2695

Bravo AF: 0.549

Asia WGS AF: 0.534 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.85
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs775748; hg19: chr3-77596460;