rs2784917

Positions:

• chr10-97169185-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.198-4295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,152 control chromosomes in the GnomAD database, including 41,459 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 0.73 (41459 hom., cov: 32)
• Consequence: SLIT1 NM_003061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

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]

ARHGAP19-SLIT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT1	NM_003061.3	c.198-4295T>C		intron_variant		ENST00000266058.9	NP_003052.2
ARHGAP19-SLIT1	NR_037909.1	n.1521-4295T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT1	ENST00000266058.9	c.198-4295T>C		intron_variant		1	NM_003061.3	ENSP00000266058	P1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111083 AN: 152034 Hom.: 41459 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.730 AC: 111108 AN: 152152 Hom.: 41459 Cov.: 32 AF XY: 0.728 AC XY: 54168 AN XY: 74376

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.751

Alfa AF: 0.761 Hom.: 8484

Bravo AF: 0.723

Asia WGS AF: 0.657 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.57

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: rs2784917; hg19: chr10-98928942;