rs3925684

Variant names:

• chr3-78651629-C-A
• rs3925684
• NM_002941.4:c.2812+103G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-78651629-C-A
• chr3-78651629-C-G

Variant summary

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

The NM_002941.4(ROBO1):​c.2812+103G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 896,032 control chromosomes in the GnomAD database, including 425,268 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 0.97 (71822 hom., cov: 32)
  • Exomes 𝑓: 0.97 (353446 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• pituitary hormone deficiency, combined or isolated, 8

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	NM_002941.4	MANE Select	c.2812+103G>T		intron	N/A	NP_002932.1	Q9Y6N7-1
	ROBO1	NM_133631.4		c.2704+103G>T		intron	N/A	NP_598334.2	Q9Y6N7-5
	ROBO1	NM_001145845.2		c.2704+103G>T		intron	N/A	NP_001139317.1	Q9Y6N7-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO1	ENST00000464233.6	TSL:5 MANE Select	c.2812+103G>T		intron	N/A	ENSP00000420321.1	Q9Y6N7-1
	ROBO1	ENST00000495273.5	TSL:1	c.2704+103G>T		intron	N/A	ENSP00000420637.1	Q9Y6N7-5
	ROBO1	ENST00000467549.5	TSL:1	c.2704+103G>T		intron	N/A	ENSP00000417992.1	Q9Y6N7-6

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147768 AN: 152166 Hom.: 71766 Cov.: 32

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.991

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.963

GnomAD4 exome AF: 0.975 AC: 724974 AN: 743748 Hom.: 353446 AF XY: 0.974 AC XY: 361148 AN XY: 370822

African (AFR) AF: 0.953 AC: 15650 AN: 16428

American (AMR) AF: 0.978 AC: 12969 AN: 13254

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 13734 AN: 14088

East Asian (EAS) AF: 1.00 AC: 28818 AN: 28820

South Asian (SAS) AF: 0.942 AC: 33378 AN: 35442

European-Finnish (FIN) AF: 0.988 AC: 38833 AN: 39302

Middle Eastern (MID) AF: 0.939 AC: 2935 AN: 3126

European-Non Finnish (NFE) AF: 0.976 AC: 545633 AN: 559296

Other (OTH) AF: 0.972 AC: 33024 AN: 33992

GnomAD4 genome AF: 0.971 AC: 147884 AN: 152284 Hom.: 71822 Cov.: 32 AF XY: 0.971 AC XY: 72305 AN XY: 74462

African (AFR) AF: 0.955 AC: 39674 AN: 41558

American (AMR) AF: 0.979 AC: 14948 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3382 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 0.943 AC: 4545 AN: 4822

European-Finnish (FIN) AF: 0.991 AC: 10525 AN: 10622

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66432 AN: 68038

Other (OTH) AF: 0.963 AC: 2037 AN: 2116

Alfa AF: 0.977 Hom.: 31038

Bravo AF: 0.971

Asia WGS AF: 0.973 AC: 3373 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
DANN	Benign	0.31
PhyloP100		-0.96
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: rs3925684; hg19: chr3-78700779;