rs12773465

Positions:

• chr10-97034302-A-G

Variant summary

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

The NM_003061.3(SLIT1):​c.2438+169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,238 control chromosomes in the GnomAD database, including 1,174 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 0.12 (1174 hom., cov: 32)
• Consequence: SLIT1 NM_003061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

Genes affected

SLIT1 (HGNC:11085): (slit guidance ligand 1) Enables Roundabout binding activity. Involved in axon extension involved in axon guidance; motor neuron axon guidance; and negative chemotaxis. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT1	NM_003061.3	c.2438+169T>C		intron_variant		ENST00000266058.9	NP_003052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT1	ENST00000266058.9	c.2438+169T>C		intron_variant		1	NM_003061.3	ENSP00000266058	P1
SLIT1	ENST00000371070.8	c.2438+169T>C		intron_variant		5		ENSP00000360109

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18124 AN: 152120 Hom.: 1177 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.119 AC: 18115 AN: 152238 Hom.: 1174 Cov.: 32 AF XY: 0.117 AC XY: 8699 AN XY: 74436

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.00636

Gnomad4 SAS AF: 0.0560

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.102

Alfa AF: 0.114 Hom.: 318

Bravo AF: 0.121

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12773465; hg19: chr10-98794059;