Genetic Variant SLIT1:p.Ala1415Ala (chr10-97002279-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003061.3(SLIT1):c.4245C>T(p.Ala1415Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,609,364 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 3 hom. )

Consequence

SLIT1
NM_003061.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.43

Publications

1 publications found

Variant links:

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]

SLIT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-97002279-G-A is Benign according to our data. Variant chr10-97002279-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640731.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.43 with no splicing effect.

BS2

High AC in GnomAd4 at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT1	NM_003061.3 link	c.4245C>T	p.Ala1415Ala	synonymous_variant	Exon 36 of 37	ENST00000266058.9	NP_003052.2	O75093-1A6H8V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT1	ENST00000266058.9 link	c.4245C>T	p.Ala1415Ala	synonymous_variant	Exon 36 of 37	1	NM_003061.3	ENSP00000266058.4		O75093-1
SLIT1	ENST00000371070.8 link	c.4242+3C>T		splice_region_variant, intron_variant	Intron 36 of 36	5		ENSP00000360109.4		Q5T0V0

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000505

AC:

121

AN:

239592

AF XY:

0.000488

show subpopulations

Gnomad AFR exome

AF:

0.0000683

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00174

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1457174

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

154

AN XY:

724500

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33454

American (AMR)

AF:

0.00176

AC:

AN:

44408

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

26038

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39628

South Asian (SAS)

AF:

0.000784

AC:

AN:

85450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51648

Middle Eastern (MID)

AF:

0.000875

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000603

AC:

AN:

1110638

Other (OTH)

AF:

0.000382

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000493

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41540

American (AMR)

AF:

0.00340

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.000194

AC:

AN:

5150

South Asian (SAS)

AF:

0.00104

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000574

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLIT1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.19

(source)

DANN

Benign

0.73

PhyloP100

-4.4

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-97002279-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over