chr4-20492638-T-A

Variant names:

• chr4-20492638-T-A
• rs525684
• NM_004787.4:c.914+739T>A

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+739T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,952 control chromosomes in the GnomAD database, including 13,675 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 0.41 (13675 hom., cov: 32)
• Consequence: SLIT2 NM_004787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT2	NM_004787.4	c.914+739T>A		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+739T>A		intron_variant	Intron 9 of 36	1	NM_004787.4	ENSP00000422591.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62269 AN: 151834 Hom.: 13673 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.410 AC: 62277 AN: 151952 Hom.: 13675 Cov.: 32 AF XY: 0.416 AC XY: 30888 AN XY: 74268

African (AFR) AF: 0.235 AC: 9724 AN: 41456

American (AMR) AF: 0.496 AC: 7568 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2737 AN: 5152

South Asian (SAS) AF: 0.451 AC: 2175 AN: 4824

European-Finnish (FIN) AF: 0.494 AC: 5211 AN: 10550

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31413 AN: 67930

Other (OTH) AF: 0.452 AC: 950 AN: 2102

Alfa AF: 0.307 Hom.: 812

Bravo AF: 0.409

Asia WGS AF: 0.484 AC: 1679 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		-0.047
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: rs525684; hg19: chr4-20494261;