NM_003061.3:c.2165-222C>T

Variant names:

• chr10-97040342-G-A
• rs3824789
• NM_003061.3:c.2165-222C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT1	NM_003061.3	MANE Select	c.2165-222C>T		intron	N/A	NP_003052.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT1	ENST00000266058.9	TSL:1 MANE Select	c.2165-222C>T		intron	N/A	ENSP00000266058.4
	SLIT1	ENST00000371070.8	TSL:5	c.2165-222C>T		intron	N/A	ENSP00000360109.4
	SLIT1	ENST00000314867.9	TSL:5	c.2144-222C>T		intron	N/A	ENSP00000315005.5

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

African (AFR) AF: 0.486 AC: 20129 AN: 41412

American (AMR) AF: 0.299 AC: 4571 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1104 AN: 3460

East Asian (EAS) AF: 0.194 AC: 1001 AN: 5158

South Asian (SAS) AF: 0.304 AC: 1459 AN: 4802

European-Finnish (FIN) AF: 0.233 AC: 2467 AN: 10592

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.314 AC: 21308 AN: 67928

Other (OTH) AF: 0.350 AC: 740 AN: 2112

Alfa AF: 0.321 Hom.: 15567

Bravo AF: 0.360

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.83
PhyloP100		-0.025
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: rs3824789; hg19: chr10-98800099;