3-79492746-T-C

Position:

• chr3-79492746-T-C

Variant summary

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

The NM_002941.4(ROBO1):​c.88+97078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,918 control chromosomes in the GnomAD database, including 10,165 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 0.36 (10165 hom., cov: 33)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.88+97078A>G		intron_variant		ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.88+97078A>G		intron_variant		5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54872 AN: 151798 Hom.: 10160 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.361 AC: 54898 AN: 151918 Hom.: 10165 Cov.: 33 AF XY: 0.361 AC XY: 26776 AN XY: 74250

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.332

Alfa AF: 0.364 Hom.: 1269

Bravo AF: 0.356

Asia WGS AF: 0.322 AC: 1110 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7622888; hg19: chr3-79541896;