chr3-78651629-C-A

Position:

• chr3-78651629-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.2812+103G>T		intron_variant		ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.2812+103G>T		intron_variant		5	NM_002941.4	ENSP00000420321	P3

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

Gnomad4 AFR exome AF: 0.953

Gnomad4 AMR exome AF: 0.978

Gnomad4 ASJ exome AF: 0.975

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.942

Gnomad4 FIN exome AF: 0.988

Gnomad4 NFE exome AF: 0.976

Gnomad4 OTH exome AF: 0.972

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

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.979

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.991

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.963

Alfa AF: 0.976 Hom.: 16768

Bravo AF: 0.971

Asia WGS AF: 0.973 AC: 3373 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs3925684; hg19: chr3-78700779;