4-20261145-T-C

Variant names:

• chr4-20261145-T-C
• rs1323067
• NM_004787.4:c.323+3206T>C

Variant summary

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

The NM_004787.4(SLIT2):​c.323+3206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,636 control chromosomes in the GnomAD database, including 34,478 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 0.67 (34478 hom., cov: 32)
• Consequence: SLIT2 NM_004787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 5 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]

SLIT2 Gene-Disease associations (from GenCC):

• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004787.4. 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
	SLIT2	NM_004787.4	MANE Select	c.323+3206T>C		intron	N/A	NP_004778.1	O94813-1
	SLIT2	NM_001289135.3		c.323+3206T>C		intron	N/A	NP_001276064.1	O94813-2
	SLIT2	NM_001289136.3		c.323+3206T>C		intron	N/A	NP_001276065.1	O94813-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT2	ENST00000504154.6	TSL:1 MANE Select	c.323+3206T>C		intron	N/A	ENSP00000422591.1	O94813-1
	SLIT2	ENST00000503837.5	TSL:1	c.323+3206T>C		intron	N/A	ENSP00000422261.1	O94813-2
	SLIT2	ENST00000503823.5	TSL:1	c.323+3206T>C		intron	N/A	ENSP00000427548.1	O94813-3

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102038 AN: 151518 Hom.: 34464 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.673 AC: 102096 AN: 151636 Hom.: 34478 Cov.: 32 AF XY: 0.677 AC XY: 50170 AN XY: 74124

African (AFR) AF: 0.689 AC: 28543 AN: 41438

American (AMR) AF: 0.703 AC: 10698 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2623 AN: 3458

East Asian (EAS) AF: 0.810 AC: 4164 AN: 5138

South Asian (SAS) AF: 0.671 AC: 3239 AN: 4828

European-Finnish (FIN) AF: 0.674 AC: 7122 AN: 10572

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43394 AN: 67668

Other (OTH) AF: 0.677 AC: 1425 AN: 2106

Alfa AF: 0.661 Hom.: 91694

Bravo AF: 0.680

Asia WGS AF: 0.722 AC: 2511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34
DANN	Benign	0.55
PhyloP100		-2.0
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: rs1323067; hg19: chr4-20262768;