rs3824789

Positions:

• chr10-97040342-G-A
• chr10-97040342-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.2165-222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,932 control chromosomes in the GnomAD database, including 10,022 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 0.35 (10022 hom., cov: 31)
• Consequence: SLIT1 NM_003061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLIT1	NM_003061.3	c.2165-222C>T		intron_variant		ENST00000266058.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLIT1	ENST00000266058.9	c.2165-222C>T		intron_variant		1	NM_003061.3	P1
SLIT1	ENST00000314867.9	c.2144-222C>T		intron_variant		5
SLIT1	ENST00000371070.8	c.2165-222C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53121 AN: 151814 Hom.: 10008 Cov.: 31

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.350 AC: 53185 AN: 151932 Hom.: 10022 Cov.: 31 AF XY: 0.344 AC XY: 25530 AN XY: 74266

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.350

Alfa AF: 0.286 Hom.: 2427

Bravo AF: 0.360

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.83

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: rs3824789; hg19: chr10-98800099;