4-20253683-G-T

Variant names:

• chr4-20253683-G-T
• rs7655084
• NM_004787.4:c.-133G>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.-133G>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 14 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=-0.8).
• 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 rank	MANE	Protein	UniProt
SLIT2	NM_004787.4	c.-133G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 37	ENST00000504154.6	NP_004778.1
SLIT2	NM_004787.4	c.-133G>T		5_prime_UTR_variant	Exon 1 of 37	ENST00000504154.6	NP_004778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT2	ENST00000504154.6	c.-133G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 37	1	NM_004787.4	ENSP00000422591.1
SLIT2	ENST00000504154.6	c.-133G>T		5_prime_UTR_variant	Exon 1 of 37	1	NM_004787.4	ENSP00000422591.1

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

African (AFR) AF: 0.839 AC: 17552 AN: 20928

American (AMR) AF: 0.803 AC: 25088 AN: 31232

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 13982 AN: 17254

East Asian (EAS) AF: 0.943 AC: 33980 AN: 36026

South Asian (SAS) AF: 0.772 AC: 47631 AN: 61676

European-Finnish (FIN) AF: 0.715 AC: 24210 AN: 33872

Middle Eastern (MID) AF: 0.769 AC: 2110 AN: 2744

European-Non Finnish (NFE) AF: 0.711 AC: 426880 AN: 600326

Other (OTH) AF: 0.751 AC: 29529 AN: 39326

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

African (AFR) AF: 0.835 AC: 34643 AN: 41464

American (AMR) AF: 0.777 AC: 11860 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2840 AN: 3470

East Asian (EAS) AF: 0.953 AC: 4863 AN: 5102

South Asian (SAS) AF: 0.778 AC: 3746 AN: 4812

European-Finnish (FIN) AF: 0.719 AC: 7594 AN: 10564

Middle Eastern (MID) AF: 0.741 AC: 215 AN: 290

European-Non Finnish (NFE) AF: 0.711 AC: 48309 AN: 67938

Other (OTH) AF: 0.763 AC: 1610 AN: 2110

Alfa AF: 0.735 Hom.: 155905

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
PhyloP100		-0.15
PromoterAI		-0.0055	Neutral
Mutation Taster		=300/0	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: rs7655084; hg19: chr4-20255306;