3-78598940-C-T

Variant names:

• chr3-78598940-C-T
• rs374513320
• NM_002941.4:c.4942-13G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_002941.4(ROBO1):​c.4942-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,533,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.95
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-78598940-C-T is Benign according to our data. Variant chr3-78598940-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1641801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000309 (47/152116) while in subpopulation SAS AF = 0.00145 (7/4822). AF 95% confidence interval is 0.00068. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.4942-13G>A		intron_variant	Intron 30 of 30	ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.4942-13G>A		intron_variant	Intron 30 of 30	5	NM_002941.4	ENSP00000420321.1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 151998 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000351 AC: 82 AN: 233342 AF XY: 0.000425

Gnomad AFR exome AF: 0.00113

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000607

Gnomad FIN exome AF: 0.0000471

Gnomad NFE exome AF: 0.0000464

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 232 AN: 1381848 Hom.: 0 Cov.: 22 AF XY: 0.000231 AC XY: 159 AN XY: 688864

African (AFR) AF: 0.000732 AC: 23 AN: 31408

American (AMR) AF: 0.0000250 AC: 1 AN: 40056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24500

East Asian (EAS) AF: 0.00103 AC: 40 AN: 38722

South Asian (SAS) AF: 0.00163 AC: 125 AN: 76668

European-Finnish (FIN) AF: 0.0000388 AC: 2 AN: 51578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4476

European-Non Finnish (NFE) AF: 0.0000312 AC: 33 AN: 1057460

Other (OTH) AF: 0.000140 AC: 8 AN: 56980

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74354

African (AFR) AF: 0.000843 AC: 35 AN: 41504

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000291

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.032
DANN	Benign	0.28
PhyloP100		-1.9

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: rs374513320; hg19: chr3-78648090;