rs11134527

Positions:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000519560.6(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 ENST00000519560.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.1459+4430C>T		intron_variant		ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.1459+4430C>T		intron_variant			NP_001258875.2
SLIT3	XM_017009779.1	c.1270+4430C>T		intron_variant			XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.1459+4430C>T		intron_variant		1	NM_003062.4	ENSP00000430333	A1
SLIT3	ENST00000332966.8	c.1459+4430C>T		intron_variant		1		ENSP00000332164	P4
SLIT3	ENST00000519486.5	n.3162+4430C>T		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.294

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.301

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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.273

Alfa AF: 0.255 Hom.: 664

Bravo AF: 0.261

Asia WGS AF: 0.504 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.87

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: rs11134527; hg19: chr5-168195356;