rs17734503

Positions:

• chr5-169039198-A-G
• chr5-169039198-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003062.4(SLIT3):​c.413+154281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,166 control chromosomes in the GnomAD database, including 4,020 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 0.19 (4020 hom., cov: 32)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.413+154281T>C		intron_variant		ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.413+154281T>C		intron_variant			NP_001258875.2
SLIT3	XM_017009779.1	c.224+154281T>C		intron_variant			XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.413+154281T>C		intron_variant		1	NM_003062.4	ENSP00000430333	A1
SLIT3	ENST00000332966.8	c.413+154281T>C		intron_variant		1		ENSP00000332164	P4
SLIT3	ENST00000518140.5	n.450+154281T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28427 AN: 152048 Hom.: 4007 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.187 AC: 28473 AN: 152166 Hom.: 4020 Cov.: 32 AF XY: 0.190 AC XY: 14105 AN XY: 74392

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.0974

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.163

Alfa AF: 0.0993 Hom.: 1147

Bravo AF: 0.200

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.73

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: rs17734503; hg19: chr5-168466203; COSMIC: COSV60599828; COSMIC: COSV60599828;