rs666088

Positions:

• chr4-20493512-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004787.4(SLIT2):​c.914+1613C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 151,990 control chromosomes in the GnomAD database, including 43,568 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 0.75 (43568 hom., cov: 32)
• Consequence: SLIT2 NM_004787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

Genes affected

SLIT2 (HGNC:11086): (slit guidance ligand 2) This gene encodes a member of the slit family of secreted glycoproteins, which are ligands for the Robo family of immunoglobulin receptors. Slit proteins play highly conserved roles in axon guidance and neuronal migration and may also have functions during other cell migration processes including leukocyte migration. Members of the slit family are characterized by an N-terminal signal peptide, four leucine-rich repeats, nine epidermal growth factor repeats, and a C-terminal cysteine knot. Proteolytic processing of this protein gives rise to an N-terminal fragment that contains the four leucine-rich repeats and five epidermal growth factor repeats and a C-terminal fragment that contains four epidermal growth factor repeats and the cysteine knot. Both full length and cleaved proteins are secreted extracellularly and can function in axon repulsion as well as other specific processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT2	NM_004787.4	c.914+1613C>T		intron_variant		ENST00000504154.6	NP_004778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT2	ENST00000504154.6	c.914+1613C>T		intron_variant		1	NM_004787.4	ENSP00000422591	P3

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114673 AN: 151870 Hom.: 43553 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.755 AC: 114732 AN: 151990 Hom.: 43568 Cov.: 32 AF XY: 0.757 AC XY: 56202 AN XY: 74260

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.775

Alfa AF: 0.737 Hom.: 47014

Bravo AF: 0.765

Asia WGS AF: 0.795 AC: 2766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.034
DANN	Benign	0.67

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: rs666088; hg19: chr4-20495135;