rs12654448

Positions:

• chr5-169054766-C-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+138713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,154 control chromosomes in the GnomAD database, including 1,627 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 0.13 (1627 hom., cov: 32)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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=-0.99).
• 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+138713G>A		intron_variant		ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.413+138713G>A		intron_variant			NP_001258875.2
SLIT3	XM_017009779.1	c.224+138713G>A		intron_variant			XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.413+138713G>A		intron_variant		1	NM_003062.4	ENSP00000430333	A1
SLIT3	ENST00000332966.8	c.413+138713G>A		intron_variant		1		ENSP00000332164	P4
SLIT3	ENST00000518140.5	n.450+138713G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19313 AN: 152036 Hom.: 1625 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.127 AC: 19323 AN: 152154 Hom.: 1627 Cov.: 32 AF XY: 0.131 AC XY: 9745 AN XY: 74390

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.118

Alfa AF: 0.106 Hom.: 155

Bravo AF: 0.131

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.65

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: rs12654448; hg19: chr5-168481771; COSMIC: COSV60599925;