10-97169185-A-G

Variant names:

• chr10-97169185-A-G
• rs2784917
• NM_003061.3:c.198-4295T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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:48348): (ARHGAP19-SLIT1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring Rho GTPase activating protein 19 (ARHGAP19) and slit homolog 1 (SLIT1) genes on chromosome 10. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003061.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT1	NM_003061.3	MANE Select	c.198-4295T>C		intron	N/A	NP_003052.2	O75093-1
	ARHGAP19-SLIT1	NR_037909.1		n.1521-4295T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT1	ENST00000266058.9	TSL:1 MANE Select	c.198-4295T>C		intron	N/A	ENSP00000266058.4	O75093-1
	ARHGAP19-SLIT1	ENST00000479633.2	TSL:2	n.1475-4295T>C		intron	N/A	ENSP00000473567.1
	SLIT1	ENST00000371070.8	TSL:5	c.198-4295T>C		intron	N/A	ENSP00000360109.4	Q5T0V0

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

African (AFR) AF: 0.572 AC: 23734 AN: 41486

American (AMR) AF: 0.757 AC: 11583 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2740 AN: 3472

East Asian (EAS) AF: 0.624 AC: 3217 AN: 5152

South Asian (SAS) AF: 0.710 AC: 3426 AN: 4822

European-Finnish (FIN) AF: 0.783 AC: 8305 AN: 10606

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55564 AN: 67992

Other (OTH) AF: 0.751 AC: 1586 AN: 2112

Alfa AF: 0.725 Hom.: 24305

Bravo AF: 0.723

Asia WGS AF: 0.657 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.57
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2784917; hg19: chr10-98928942;