chr4-20253683-G-T

Position:

• chr4-20253683-G-T

Variant summary

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

The NM_004787.4(SLIT2):​c.-133G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 995,306 control chromosomes in the GnomAD database, including 275,688 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 0.77 (44928 hom., cov: 30)
  • Exomes 𝑓: 0.74 (230760 hom.)
• Consequence: SLIT2 NM_004787.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT2	NM_004787.4	c.-133G>T		5_prime_UTR_variant	1/37	ENST00000504154.6	NP_004778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT2	ENST00000504154.6	c.-133G>T		5_prime_UTR_variant	1/37	1	NM_004787.4	ENSP00000422591	P3
SLIT2	ENST00000503823.5	c.-133G>T		5_prime_UTR_variant	1/36	1		ENSP00000427548	A1
SLIT2	ENST00000273739.9	c.-133G>T		5_prime_UTR_variant	1/39	5		ENSP00000273739
SLIT2	ENST00000622093.4	c.-391G>T		5_prime_UTR_variant	1/37	5		ENSP00000482129

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116347 AN: 151804 Hom.: 44898 Cov.: 30

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.740

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.736 AC: 620962 AN: 843384 Hom.: 230760 Cov.: 11 AF XY: 0.737 AC XY: 317703 AN XY: 431286

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.803

Gnomad4 ASJ exome AF: 0.810

Gnomad4 EAS exome AF: 0.943

Gnomad4 SAS exome AF: 0.772

Gnomad4 FIN exome AF: 0.715

Gnomad4 NFE exome AF: 0.711

Gnomad4 OTH exome AF: 0.751

GnomAD4 genome AF: 0.766 AC: 116431 AN: 151922 Hom.: 44928 Cov.: 30 AF XY: 0.768 AC XY: 57056 AN XY: 74262

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.763

Alfa AF: 0.730 Hom.: 64510

Bravo AF: 0.778

Asia WGS AF: 0.842 AC: 2928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.86

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: rs7655084; hg19: chr4-20255306;