rs6548592

chr3-78631428-T-Cchr3-78631428-T-G

Variant summary

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

The NM_002941.4(ROBO1):c.3482-123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 1,055,962 control chromosomes in the GnomAD database, including 130,613 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 0.51 (19965 hom., cov: 32)
  • Exomes 𝑓: 0.49 (110648 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

ROBO1 (HGNC:10249): (roundabout guidance receptor 1) Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The product of this gene is a member of the immunoglobulin gene superfamily and encodes an integral membrane protein that functions in axon guidance and neuronal precursor cell migration. This receptor is activated by SLIT-family proteins, resulting in a repulsive effect on glioma cell guidance in the developing brain. A related gene is located at an adjacent region on chromosome 3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO1	NM_002941.4	c.3482-123A>G		intron_variant		ENST00000464233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO1	ENST00000464233.6	c.3482-123A>G		intron_variant		5	NM_002941.4	P3

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77222 AN: 151922 Hom.: 19959 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.489 AC: 441959 AN: 903920 Hom.: 110648 AF XY: 0.489 AC XY: 218900 AN XY: 447782

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.508 AC: 77255 AN: 152042 Hom.: 19965 Cov.: 32 AF XY: 0.506 AC XY: 37625 AN XY: 74304

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.520

Alfa AF: 0.502 Hom.: 2338

Bravo AF: 0.512

Asia WGS AF: 0.399 AC: 1390 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.20
Dann	Benign	0.77

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: rs6548592; hg19: chr3-78680578; COSMIC: COSV71397154;