rs11134527

Variant names:

• chr5-168768351-G-A
• rs11134527
• NM_003062.4:c.1459+4430C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-168768351-G-A
• chr5-168768351-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003062.4(SLIT3):​c.1459+4430C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 459,298 control chromosomes in the GnomAD database, including 23,653 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 0.26 (5906 hom., cov: 32)
  • Exomes 𝑓: 0.32 (17747 hom.)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 73 publications found

Genes affected

SLIT3 (HGNC:11087): (slit guidance ligand 3) The protein encoded by this gene is secreted, likely interacting with roundabout homolog receptors to effect cell migration. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

MIR218-2 (HGNC:31596): (microRNA 218-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	NM_003062.4	MANE Select	c.1459+4430C>T		intron	N/A	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.1459+4430C>T		intron	N/A	NP_001258875.2	O75094-4
	MIR218-2	NR_029632.1		n.-96C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	ENST00000519560.6	TSL:1 MANE Select	c.1459+4430C>T		intron	N/A	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.1459+4430C>T		intron	N/A	ENSP00000332164.8	O75094-4
	SLIT3	ENST00000519486.5	TSL:1	n.3162+4430C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39456 AN: 151926 Hom.: 5918 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.323 AC: 99096 AN: 307254 Hom.: 17747 AF XY: 0.333 AC XY: 58207 AN XY: 174676

African (AFR) AF: 0.152 AC: 1303 AN: 8588

American (AMR) AF: 0.437 AC: 11882 AN: 27170

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 3213 AN: 10736

East Asian (EAS) AF: 0.570 AC: 5254 AN: 9214

South Asian (SAS) AF: 0.450 AC: 26827 AN: 59678

European-Finnish (FIN) AF: 0.294 AC: 4769 AN: 16202

Middle Eastern (MID) AF: 0.309 AC: 831 AN: 2692

European-Non Finnish (NFE) AF: 0.257 AC: 40727 AN: 158706

Other (OTH) AF: 0.301 AC: 4290 AN: 14268

GnomAD4 genome AF: 0.260 AC: 39457 AN: 152044 Hom.: 5906 Cov.: 32 AF XY: 0.268 AC XY: 19951 AN XY: 74318

African (AFR) AF: 0.153 AC: 6343 AN: 41486

American (AMR) AF: 0.347 AC: 5298 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2907 AN: 5148

South Asian (SAS) AF: 0.458 AC: 2206 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3204 AN: 10568

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17450 AN: 67970

Other (OTH) AF: 0.273 AC: 577 AN: 2116

Alfa AF: 0.259 Hom.: 7906

Bravo AF: 0.261

Asia WGS AF: 0.504 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.87
PhyloP100		0.59
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: rs11134527; hg19: chr5-168195356;