3-76672262-T-G

Position:

• chr3-76672262-T-G

Variant summary

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

The NM_001394212.1(ROBO2):​c.130+360845T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,650 control chromosomes in the GnomAD database, including 9,066 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 0.33 (9066 hom., cov: 30)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO2	NM_001128929.3	c.110-425752T>G		intron_variant			NP_001122401.1
ROBO2	NM_001378190.1	c.110-425752T>G		intron_variant			NP_001365119.1
ROBO2	NM_001378191.1	c.110-425752T>G		intron_variant			NP_001365120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000471893.2	c.110-425752T>G		intron_variant		4		ENSP00000418190
ROBO2	ENST00000475334.2	c.130+360845T>G		intron_variant		5		ENSP00000418446	A1
ROBO2	ENST00000487694.7	c.110-425752T>G		intron_variant		5		ENSP00000417335

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49898 AN: 151530 Hom.: 9075 Cov.: 30

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.329 AC: 49891 AN: 151650 Hom.: 9066 Cov.: 30 AF XY: 0.329 AC XY: 24405 AN XY: 74114

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.361

Alfa AF: 0.384 Hom.: 22923

Bravo AF: 0.329

Asia WGS AF: 0.431 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1349008; hg19: chr3-76721413;