rs1379659

Positions:

• chr4-20619060-G-A
• chr4-20619060-G-C

Variant summary

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

The NM_004787.4(SLIT2):​c.*51G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,563,458 control chromosomes in the GnomAD database, including 527,498 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 0.86 (56928 hom., cov: 30)
  • Exomes 𝑓: 0.82 (470570 hom.)
• Consequence: SLIT2 NM_004787.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT2	NM_004787.4	c.*51G>A		3_prime_UTR_variant	37/37	ENST00000504154.6	NP_004778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT2	ENST00000504154.6	c.*51G>A		3_prime_UTR_variant	37/37	1	NM_004787.4	ENSP00000422591	P3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131047 AN: 151972 Hom.: 56864 Cov.: 30

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.865

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.862

GnomAD3 exomes AF: 0.846 AC: 203051 AN: 239992 Hom.: 86251 AF XY: 0.844 AC XY: 109007 AN XY: 129196

Gnomad AFR exome AF: 0.968

Gnomad AMR exome AF: 0.914

Gnomad ASJ exome AF: 0.841

Gnomad EAS exome AF: 0.833

Gnomad SAS exome AF: 0.883

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.807

Gnomad OTH exome AF: 0.834

GnomAD4 exome AF: 0.816 AC: 1151074 AN: 1411364 Hom.: 470570 Cov.: 24 AF XY: 0.817 AC XY: 567868 AN XY: 695252

Gnomad4 AFR exome AF: 0.971

Gnomad4 AMR exome AF: 0.914

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.809

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.862 AC: 131175 AN: 152094 Hom.: 56928 Cov.: 30 AF XY: 0.865 AC XY: 64297 AN XY: 74328

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.861

Alfa AF: 0.817 Hom.: 92495

Bravo AF: 0.870

Asia WGS AF: 0.864 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.013
DANN	Benign	0.71

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: rs1379659; hg19: chr4-20620683;