5-168764061-T-C

Variant names:

• chr5-168764061-T-C
• rs11745421
• NM_003062.4:c.1460-1372A>G

Variant summary

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

The NM_003062.4(SLIT3):​c.1460-1372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 152,282 control chromosomes in the GnomAD database, including 525 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 0.079 (525 hom., cov: 32)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• Publications: 2 publications found

Genes affected

SLIT3 (HGNC:11087): (slit guidance ligand 3) The protein encoded by this gene is secreted, likely interacting with roundabout homolog receptors to effect cell migration. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.1460-1372A>G		intron_variant	Intron 14 of 35	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.1460-1372A>G		intron_variant	Intron 14 of 35		NP_001258875.2
SLIT3	XM_017009779.1	c.1271-1372A>G		intron_variant	Intron 14 of 35		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.1460-1372A>G		intron_variant	Intron 14 of 35	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.1460-1372A>G		intron_variant	Intron 14 of 35	1		ENSP00000332164.8
SLIT3	ENST00000519486.5	n.3163-1372A>G		intron_variant	Intron 4 of 7	1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12038 AN: 152164 Hom.: 524 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0791 AC: 12052 AN: 152282 Hom.: 525 Cov.: 32 AF XY: 0.0766 AC XY: 5705 AN XY: 74474

African (AFR) AF: 0.0766 AC: 3185 AN: 41556

American (AMR) AF: 0.0724 AC: 1108 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0385 AC: 186 AN: 4828

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0916 AC: 6230 AN: 68018

Other (OTH) AF: 0.0915 AC: 193 AN: 2110

Alfa AF: 0.0910 Hom.: 1143

Bravo AF: 0.0816

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.47
PhyloP100		-0.40
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: rs11745421; hg19: chr5-168191066; COSMIC: COSV60598350; COSMIC: COSV60598350;