rs2817677

Positions:

• chr10-97062071-G-A
• chr10-97062071-G-T

Variant summary

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

The NM_003061.3(SLIT1):​c.794-1284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,090 control chromosomes in the GnomAD database, including 28,201 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 0.58 (28201 hom., cov: 33)
• Consequence: SLIT1 NM_003061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT1	NM_003061.3	c.794-1284C>T		intron_variant		ENST00000266058.9	NP_003052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT1	ENST00000266058.9	c.794-1284C>T		intron_variant		1	NM_003061.3	ENSP00000266058	P1
SLIT1	ENST00000314867.9	c.743-1284C>T		intron_variant		5		ENSP00000315005
SLIT1	ENST00000371041.3	c.794-1284C>T		intron_variant		2		ENSP00000360080
SLIT1	ENST00000371070.8	c.794-1284C>T		intron_variant		5		ENSP00000360109

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88456 AN: 151972 Hom.: 28194 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.582 AC: 88468 AN: 152090 Hom.: 28201 Cov.: 33 AF XY: 0.590 AC XY: 43917 AN XY: 74382

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.596

Alfa AF: 0.649 Hom.: 16433

Bravo AF: 0.567

Asia WGS AF: 0.621 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2817677; hg19: chr10-98821828;