rs3849491

Positions:

• chr3-76435032-T-C
• chr3-76435032-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+123615T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,343,278 control chromosomes in the GnomAD database, including 180,139 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 0.46 (16932 hom., cov: 32)
  • Exomes 𝑓: 0.52 (163207 hom.)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+123615T>C		intron_variant			NP_001381141.1
ROBO2	NM_001378191.1	c.109+497430T>C		intron_variant			NP_001365120.1
ROBO2	NM_001378192.1	c.130+123615T>C		intron_variant			NP_001365121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.109+497430T>C		intron_variant				ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+497430T>C		intron_variant				ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+497430T>C		intron_variant		4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70160 AN: 151866 Hom.: 16925 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.520 AC: 619603 AN: 1191294 Hom.: 163207 Cov.: 17 AF XY: 0.523 AC XY: 316977 AN XY: 606056

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.594

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.520

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.462 AC: 70200 AN: 151984 Hom.: 16932 Cov.: 32 AF XY: 0.467 AC XY: 34670 AN XY: 74280

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.460

Alfa AF: 0.476 Hom.: 6638

Bravo AF: 0.445

Asia WGS AF: 0.468 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3849491; hg19: chr3-76484183; COSMIC: COSV72102297;