rs7623809

Variant names:

• chr3-79519823-A-G
• rs7623809
• NM_002941.4:c.88+70001T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-79519823-A-G
• chr3-79519823-A-T

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+70001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 151,488 control chromosomes in the GnomAD database, including 41,348 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 0.73 (41348 hom., cov: 28)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.88+70001T>C		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+70001T>C		intron_variant	Intron 2 of 30	5	NM_002941.4	ENSP00000420321.1
ROBO1	ENST00000492990.1	n.*210+6669T>C		intron_variant	Intron 4 of 4	3		ENSP00000419915.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110247 AN: 151370 Hom.: 41282 Cov.: 28

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.729 AC: 110378 AN: 151488 Hom.: 41348 Cov.: 28 AF XY: 0.724 AC XY: 53559 AN XY: 73980

African (AFR) AF: 0.921 AC: 38066 AN: 41322

American (AMR) AF: 0.641 AC: 9719 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2118 AN: 3464

East Asian (EAS) AF: 0.674 AC: 3439 AN: 5102

South Asian (SAS) AF: 0.560 AC: 2685 AN: 4794

European-Finnish (FIN) AF: 0.691 AC: 7231 AN: 10460

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44955 AN: 67884

Other (OTH) AF: 0.694 AC: 1451 AN: 2090

Alfa AF: 0.707 Hom.: 5047

Bravo AF: 0.737

Asia WGS AF: 0.627 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		-0.30
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: rs7623809; hg19: chr3-79568973;