4-20619060-G-A

Variant names:

• chr4-20619060-G-A
• rs1379659
• NM_004787.4:c.*51G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004787.4(SLIT2):​c.*51G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,563,458 control chromosomes in the GnomAD database, including 527,498 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 0.86 (56928 hom., cov: 30)
  • Exomes 𝑓: 0.82 (470570 hom.)
• Consequence: SLIT2 NM_004787.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004787.4. 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
	SLIT2	NM_004787.4	MANE Select	c.*51G>A		3_prime_UTR	Exon 37 of 37	NP_004778.1
	SLIT2	NM_001289135.3		c.*51G>A		3_prime_UTR	Exon 37 of 37	NP_001276064.1
	SLIT2	NM_001289136.3		c.*51G>A		3_prime_UTR	Exon 36 of 36	NP_001276065.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT2	ENST00000504154.6	TSL:1 MANE Select	c.*51G>A		3_prime_UTR	Exon 37 of 37	ENSP00000422591.1
	SLIT2	ENST00000503837.5	TSL:1	c.*51G>A		3_prime_UTR	Exon 37 of 37	ENSP00000422261.1
	SLIT2	ENST00000503823.5	TSL:1	c.*51G>A		3_prime_UTR	Exon 36 of 36	ENSP00000427548.1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131047 AN: 151972 Hom.: 56864 Cov.: 30

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.865

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.862

GnomAD2 exomes AF: 0.846 AC: 203051 AN: 239992 AF XY: 0.844

Gnomad AFR exome AF: 0.968

Gnomad AMR exome AF: 0.914

Gnomad ASJ exome AF: 0.841

Gnomad EAS exome AF: 0.833

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.807

Gnomad OTH exome AF: 0.834

GnomAD4 exome AF: 0.816 AC: 1151074 AN: 1411364 Hom.: 470570 Cov.: 24 AF XY: 0.817 AC XY: 567868 AN XY: 695252

African (AFR) AF: 0.971 AC: 31775 AN: 32716

American (AMR) AF: 0.914 AC: 39556 AN: 43286

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 20557 AN: 24622

East Asian (EAS) AF: 0.844 AC: 32761 AN: 38806

South Asian (SAS) AF: 0.882 AC: 71300 AN: 80868

European-Finnish (FIN) AF: 0.809 AC: 42572 AN: 52614

Middle Eastern (MID) AF: 0.839 AC: 4677 AN: 5576

European-Non Finnish (NFE) AF: 0.800 AC: 860118 AN: 1074628

Other (OTH) AF: 0.820 AC: 47758 AN: 58248

GnomAD4 genome AF: 0.862 AC: 131175 AN: 152094 Hom.: 56928 Cov.: 30 AF XY: 0.865 AC XY: 64297 AN XY: 74328

African (AFR) AF: 0.963 AC: 40000 AN: 41518

American (AMR) AF: 0.884 AC: 13516 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2883 AN: 3468

East Asian (EAS) AF: 0.849 AC: 4385 AN: 5164

South Asian (SAS) AF: 0.875 AC: 4216 AN: 4816

European-Finnish (FIN) AF: 0.815 AC: 8607 AN: 10560

Middle Eastern (MID) AF: 0.870 AC: 254 AN: 292

European-Non Finnish (NFE) AF: 0.805 AC: 54747 AN: 67970

Other (OTH) AF: 0.861 AC: 1817 AN: 2110

Alfa AF: 0.828 Hom.: 152868

Bravo AF: 0.870

Asia WGS AF: 0.864 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.013
DANN	Benign	0.71
PhyloP100		-2.3
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: rs1379659; hg19: chr4-20620683;