rs331142

Variant names:

• chr3-78871694-C-A
• rs331142
• NM_002941.4:c.499+66907G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-78871694-C-A
• chr3-78871694-C-G
• chr3-78871694-C-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.499+66907G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 148,138 control chromosomes in the GnomAD database, including 36,822 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 0.70 (36822 hom., cov: 24)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.499+66907G>T		intron_variant	Intron 4 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.499+66907G>T		intron_variant	Intron 4 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 104094 AN: 148042 Hom.: 36800 Cov.: 24

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.781

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.703 AC: 104151 AN: 148138 Hom.: 36822 Cov.: 24 AF XY: 0.701 AC XY: 50516 AN XY: 72016

African (AFR) AF: 0.644 AC: 25867 AN: 40188

American (AMR) AF: 0.697 AC: 10318 AN: 14812

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2746 AN: 3464

East Asian (EAS) AF: 0.542 AC: 2719 AN: 5014

South Asian (SAS) AF: 0.710 AC: 3332 AN: 4694

European-Finnish (FIN) AF: 0.701 AC: 6541 AN: 9332

Middle Eastern (MID) AF: 0.777 AC: 219 AN: 282

European-Non Finnish (NFE) AF: 0.745 AC: 50246 AN: 67426

Other (OTH) AF: 0.704 AC: 1427 AN: 2026

Alfa AF: 0.731 Hom.: 21830

Bravo AF: 0.696

Asia WGS AF: 0.615 AC: 2129 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.58
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs331142; hg19: chr3-78920844;