rs1880646

Positions:

• chr17-9026528-A-G
• chr17-9026528-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000173229.7(NTN1):​c.1018+3137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,900 control chromosomes in the GnomAD database, including 7,112 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 0.30 (7112 hom., cov: 31)
• Consequence: NTN1 ENST00000173229.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

Genes affected

NTN1 (HGNC:8029): (netrin 1) Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1018+3137A>G		intron_variant		ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1018+3137A>G		intron_variant			XP_006721658.1
NTN1	XM_047437096.1	c.1018+3137A>G		intron_variant			XP_047293052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN1	ENST00000173229.7	c.1018+3137A>G		intron_variant		1	NM_004822.3	ENSP00000173229	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45762 AN: 151782 Hom.: 7110 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.301 AC: 45771 AN: 151900 Hom.: 7112 Cov.: 31 AF XY: 0.301 AC XY: 22338 AN XY: 74226

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.324

Alfa AF: 0.273 Hom.: 3114

Bravo AF: 0.304

Asia WGS AF: 0.419 AC: 1456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs1880646; hg19: chr17-8929845;