4-20493512-C-T

Variant names:

• chr4-20493512-C-T
• rs666088
• NM_004787.4:c.914+1613C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLIT2	NM_004787.4	c.914+1613C>T		intron_variant	Intron 9 of 36	ENST00000504154.6	NP_004778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT2	ENST00000504154.6	c.914+1613C>T		intron_variant	Intron 9 of 36	1	NM_004787.4	ENSP00000422591.1

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

African (AFR) AF: 0.799 AC: 33121 AN: 41452

American (AMR) AF: 0.772 AC: 11776 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2813 AN: 3470

East Asian (EAS) AF: 0.953 AC: 4915 AN: 5160

South Asian (SAS) AF: 0.701 AC: 3365 AN: 4802

European-Finnish (FIN) AF: 0.733 AC: 7734 AN: 10554

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48406 AN: 67978

Other (OTH) AF: 0.775 AC: 1634 AN: 2108

Alfa AF: 0.736 Hom.: 117313

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
PhyloP100		-2.7
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: rs666088; hg19: chr4-20495135;