5-168764061-T-C

Variant summary

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

The NM_003062.4(SLIT3):c.1460-1372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 152,282 control chromosomes in the GnomAD database, including 525 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 0.079 (525 hom., cov: 32)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLIT3	NM_003062.4	c.1460-1372A>G		intron_variant		ENST00000519560.6
SLIT3	NM_001271946.2	c.1460-1372A>G		intron_variant
SLIT3	XM_017009779.1	c.1271-1372A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLIT3	ENST00000519560.6	c.1460-1372A>G		intron_variant		1	NM_003062.4	A1
SLIT3	ENST00000332966.8	c.1460-1372A>G		intron_variant		1		P4
SLIT3	ENST00000519486.5	n.3163-1372A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12038 AN: 152164 Hom.: 524 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0791 AC: 12052 AN: 152282 Hom.: 525 Cov.: 32 AF XY: 0.0766 AC XY: 5705 AN XY: 74474

Gnomad4 AFR AF: 0.0766

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0385

Gnomad4 FIN AF: 0.0445

Gnomad4 NFE AF: 0.0916

Gnomad4 OTH AF: 0.0915

Alfa AF: 0.0914 Hom.: 890

Bravo AF: 0.0816

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.42
Dann	Benign	0.47

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: rs11745421; hg19: chr5-168191066; COSMIC: COSV60598350; COSMIC: COSV60598350;