Variant chr4-20253997-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004787.4(SLIT2):c.179+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,600,262 control chromosomes in the GnomAD database, including 700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 33 hom., cov: 32)

Exomes 𝑓: 0.019 ( 667 hom. )

Consequence

SLIT2
NM_004787.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0002278

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.981

Variant links:

Genes affected

SLIT2 (HGNC:11086): (slit guidance ligand 2) This gene encodes a member of the slit family of secreted glycoproteins, which are ligands for the Robo family of immunoglobulin receptors. Slit proteins play highly conserved roles in axon guidance and neuronal migration and may also have functions during other cell migration processes including leukocyte migration. Members of the slit family are characterized by an N-terminal signal peptide, four leucine-rich repeats, nine epidermal growth factor repeats, and a C-terminal cysteine knot. Proteolytic processing of this protein gives rise to an N-terminal fragment that contains the four leucine-rich repeats and five epidermal growth factor repeats and a C-terminal fragment that contains four epidermal growth factor repeats and the cysteine knot. Both full length and cleaved proteins are secreted extracellularly and can function in axon repulsion as well as other specific processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

SLIT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 4-20253997-G-A is Benign according to our data. Variant chr4-20253997-G-A is described in ClinVar as [Benign]. Clinvar id is 1598728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLIT2	NM_004787.4 linkuse as main transcript	c.179+3G>A		splice_donor_region_variant, intron_variant		ENST00000504154.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLIT2	ENST00000504154.6 linkuse as main transcript	c.179+3G>A		splice_donor_region_variant, intron_variant		1	NM_004787.4	P3	O94813-1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2221

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00886

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00806

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0184

Gnomad SAS

AF:

0.0991

Gnomad FIN

AF:

0.00933

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0234

AC:

5670

AN:

241792

Hom.:

212

AF XY:

0.0274

AC XY:

3602

AN XY:

131324

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.00451

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.0219

Gnomad SAS exome

AF:

0.0972

Gnomad FIN exome

AF:

0.00909

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0167

GnomAD4 exome

AF:

0.0189

AC:

27424

AN:

1448124

Hom.:

667

Cov.:

AF XY:

0.0213

AC XY:

15311

AN XY:

720326

show subpopulations

Gnomad4 AFR exome

AF:

0.00806

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.00474

Gnomad4 EAS exome

AF:

0.0282

Gnomad4 SAS exome

AF:

0.0951

Gnomad4 FIN exome

AF:

0.00825

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0191

GnomAD4 genome

AF:

0.0146

AC:

2224

AN:

152138

Hom.:

Cov.:

AF XY:

0.0157

AC XY:

1168

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00881

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.0182

Gnomad4 SAS

AF:

0.0998

Gnomad4 FIN

AF:

0.00933

Gnomad4 NFE

AF:

0.0148

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

EpiCase

AF:

0.0151

EpiControl

AF:

0.0143

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over