chr4-20423151-C-G

Variant names:

• chr4-20423151-C-G
• rs1995982
• NM_004787.4:c.396-44601C>G

Variant summary

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

The NM_004787.4(SLIT2):​c.396-44601C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,838 control chromosomes in the GnomAD database, including 41,628 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 0.74 (41628 hom., cov: 30)
• Consequence: SLIT2 NM_004787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT2	NM_004787.4	c.396-44601C>G		intron_variant	Intron 4 of 36	ENST00000504154.6	NP_004778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT2	ENST00000504154.6	c.396-44601C>G		intron_variant	Intron 4 of 36	1	NM_004787.4	ENSP00000422591.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111809 AN: 151720 Hom.: 41577 Cov.: 30

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.737 AC: 111919 AN: 151838 Hom.: 41628 Cov.: 30 AF XY: 0.733 AC XY: 54347 AN XY: 74192

African (AFR) AF: 0.834 AC: 34525 AN: 41406

American (AMR) AF: 0.730 AC: 11123 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2736 AN: 3468

East Asian (EAS) AF: 0.538 AC: 2765 AN: 5136

South Asian (SAS) AF: 0.568 AC: 2735 AN: 4814

European-Finnish (FIN) AF: 0.729 AC: 7680 AN: 10536

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47980 AN: 67942

Other (OTH) AF: 0.743 AC: 1564 AN: 2106

Alfa AF: 0.658 Hom.: 1919

Bravo AF: 0.745

Asia WGS AF: 0.606 AC: 2108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.44
PhyloP100		-0.95
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: rs1995982; hg19: chr4-20424774;