rs6803202

Variant names:

• chr3-79450003-C-T
• rs6803202
• NM_002941.4:c.88+139821G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002941.4(ROBO1):​c.88+139821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,624 control chromosomes in the GnomAD database, including 19,618 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 (19618 hom., cov: 31)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 10 publications found

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]

ROBO1 Gene-Disease associations (from GenCC):

• neurooculorenal syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary hormone deficiency, combined or isolated, 8

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288105 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.88+139821G>A		intron_variant	Intron 2 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.88+139821G>A		intron_variant	Intron 2 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76808 AN: 151506 Hom.: 19613 Cov.: 31

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.507 AC: 76842 AN: 151624 Hom.: 19618 Cov.: 31 AF XY: 0.505 AC XY: 37396 AN XY: 74066

African (AFR) AF: 0.565 AC: 23361 AN: 41328

American (AMR) AF: 0.429 AC: 6526 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1667 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1967 AN: 5136

South Asian (SAS) AF: 0.499 AC: 2398 AN: 4806

European-Finnish (FIN) AF: 0.507 AC: 5301 AN: 10464

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34116 AN: 67902

Other (OTH) AF: 0.498 AC: 1051 AN: 2112

Alfa AF: 0.502 Hom.: 41268

Bravo AF: 0.499

Asia WGS AF: 0.430 AC: 1497 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	1.3
DANN	Benign	0.41
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6803202; hg19: chr3-79499153;