chr3-76434240-G-A

Variant names:

• chr3-76434240-G-A
• rs10514733
• NM_001394212.1:c.130+122823G>A

Variant summary

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

The NM_001394212.1(ROBO2):​c.130+122823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,015,188 control chromosomes in the GnomAD database, including 781 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 0.024 (90 hom., cov: 32)
  • Exomes 𝑓: 0.023 (691 hom.)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

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]

CAP1P1 (HGNC:31134): (CAP1 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+122823G>A		intron_variant	Intron 1 of 27		NP_001381141.1
ROBO2	NM_001378191.1	c.109+496638G>A		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378192.1	c.130+122823G>A		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+496638G>A		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+496638G>A		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+496638G>A		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3692 AN: 152192 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0278

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.0234 AC: 20229 AN: 862878 Hom.: 691 Cov.: 13 AF XY: 0.0260 AC XY: 11777 AN XY: 453682

Gnomad4 AFR exome AF: 0.0346

Gnomad4 AMR exome AF: 0.0739

Gnomad4 ASJ exome AF: 0.0503

Gnomad4 EAS exome AF: 0.0343

Gnomad4 SAS exome AF: 0.0960

Gnomad4 FIN exome AF: 0.00152

Gnomad4 NFE exome AF: 0.00958

Gnomad4 OTH exome AF: 0.0259

GnomAD4 genome AF: 0.0244 AC: 3716 AN: 152310 Hom.: 90 Cov.: 32 AF XY: 0.0264 AC XY: 1964 AN XY: 74472

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.0279

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0177 Hom.: 56

Bravo AF: 0.0265

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514733; hg19: chr3-76483391; COSMIC: COSV72102528;